sedoheptulose bisphosphate bypass

MetaCyc:PWY0-1517

This ATP-dependent two-event bypass converts sedoheptulose7-phosphate (S7P) through sedoheptulose1, 7-bisphosphate (SBP) to erythrose4-phosphate (E4P) and glycerone phosphate (DHAP). Exact Rhea chemistry is S7P + ATP -> SBP + ADP + H(+), followed by SBP -> E4P + DHAP. Native RXN0-6541 and SEDOBISALDOL-RXN map to directional RHEA31444 and cleavage30169; native 30170 is bidirectional and 30168 is condensation. The generic S7P class is distinct from alpha-pyranose CPD-19339/CHEBI133984. PfkA is a native homotetramer and FbaA a homodimer, not the mixed PfkA/PfkB assembly suggested by the frozen PathBank component list. Reference P0A796/b3916 and P0AB71/b2925 and MG1655 GeneIDs948412/947415 anchor identity; off-taxon GeneIDs93777982/93779073 belong to Shigella sonnei and are rejected. Database taxonomic range and reference identity do not establish unmodified wild-type flux in every strain. [EcoCyc:6PFK-1-CPX; EcoCyc:FRUCBISALD-CLASSII; EcoCyc:PWY0-1517; Entrez:947415; Entrez:948412; MetaCyc:CPD-19339; MetaCyc:D-SEDOHEPTULOSE-1-7-P2; MetaCyc:D-SEDOHEPTULOSE-7-P; MetaCyc:PWY0-1517; MetaCyc:RXN0-6541; MetaCyc:SEDOBISALDOL-RXN; PathBank:SMP0002110; RHEA:30169; RHEA:31444; UniProtKB:P0A796; UniProtKB:P0AB71] PMID19756045 studies BW25113 talA:tet/talB:Cm derivatives, not a sequenced MG1655 assay strain. The double deletion grows on xylose (doubling time110 min versus 100 min wild type); additional pfkA deletion abolishes this growth. deoBC, fbp and tpiA comparisons distinguish alternative routes, with the paper's data-not-shown limitations retained. Growth screening, metabolomics and enzyme assays have distinct media/carbon concentrations. Cultures were at 37 °C, generally in MOPS medium; a common universal medium is not inferred. [PMID:19756045] The 2009 direct assay uses six-His ASKA PfkA/FbaA, 2 µM enzyme, 5 mM S7P or F6P, 2 mM ATP and 50 mM potassium MOPS at 37 °C for 1 h (five samples). TableIII separates no-enzyme S7P 5.13±0.26 mM with products not detected; PfkA-only S7P 2.91±0.15/SBP 1.15±0.13; both enzymes S7P 3.05±0.14/SBP 0.79±0.11/DHAP0.23±0.02/E4P0.39±0.03; FbaA-only S7P 5.27±0.17 with products not detected; and the F6P comparison yielding FBP/DHAP with E4P not determined. No authentic SBP standard was available: migration reasoning and F1, 6BP calibration were used. Results report m/z369.0 and Methods367.0, an unresolved internal discrepancy rather than a silently corrected observation. [PMID:19756045] The 2009 original supplementary workbooks retain S7P accumulation of about 45.67-fold on xylose and 101.63-fold on gluconate for the selected mutant/wild-type columns. The description of no notable transcriptional change differs from literal equality: fbaA ratio 1.18 and pfkA1.241 are retained. Isotopomer model fits support the bypass in tested talAB cells; with uptake normalized100, wild-type best-fit bypass values are small nonzero0.004/0.005 and the mutant both-pathway fit is about 29.923/29.181. These are model-specific relative fluxes. Some supplementary MFA equations label the SBP-cleavage product GAP/G3P rather than DHAP; direct products and Rhea define the chemistry, and no TPI event is added to repair a source model. [PMID:19756045] Supplementary Figure 8 of PMID19756045 uses the Lactococcus lactis pfk ORF in pTRC99A under a trc promoter to complement the E. coli talAB pfkA triple-mutant xylose phenotype (MOPS, 0.2% xylose, 1 mM IPTG). The donor strain/accession is not supplied. This is heterologous complementation, not native L. lactis complete-pathway flux or a reference-protein sequence assignment. [PMID:19756045] PMID31871051 reconstructs BW25113 talAB and measures xylose growth at 0.33±0.01 h−1 versus wild type 0.39±0.01 in M9; glucose values are0.52 versus 0.49 h−1. Its knockout Methods inconsistently mention pKD3 and pKD4. Orbitrap identification at 368.99 [M-H]− with 199/271 fragments uses mutant extract as a control, not an authentic commercial SBP standard. SBP stability limits, a blank368.804 peak and trace wild-type xylose SBP remain explicit; metabolite detection does not measure wild-type bypass flux. Its PfkA BW25113_3916 in pET-28b(+), DH5α cloning, Rosetta expression and His-affinity purification is separate from the 2009 ASKA preparation. [PMID:31871051] The 2020 E. coli PfkA comparison at 55 °C reports F6P apparent Km 0.065 mM/kcat 1.2 s−1 versus S7P 2.5 mM/0.25 s−1. Tabulated S7P efficiency0.15×10^3 differs from arithmetic using the rounded values and is not replaced. The coupled assay includes Mg 5 mM, ATP 2 mM, ADP 0.25 mM, rabbit aldolase4 U/ml, G3PDH2 U/ml and NADH0.15 mM. S7P was supplied as a Ba salt; this reagent form is retained as assay context, not a new core species. No TPI was added; trace TPI is a suggested explanation for unequal downstream peaks, not a new E. coli core participant. The separately cited2020 thesis DOI10.18174/510683 chapter6 supplement is not asserted byte-identical to the inaccessible journal supplement. PDF137 FigureS1 is a no-enzyme control; PDF140 FigureS4 shows both Michaelis–Menten S7P Km 2.489181822 mM and Hill K1/2=1.24179394 mM, n=1.603138135. Raw Vmax in dAbs/min is not kcat, and the fit comparison does not establish physiological bypass cooperativity. [DOI:10.18174/510683; PMID:31871051] The clostridial PPi-dependent six-event MetaCycPWY-8178 definition is a separate pathway. Added rabbit aldolase in the 2020 coupling assay does not characterize a particular native clostridial aldolase. C. thermosuccinogenes ATP/GTP-PFK CDQ83_07225 showed no S7P activity up to 4 mM; its F6P ammonium dependence, very high Hill coefficient and proposed relief-valve role concern another enzyme and remain a hypothesis. The later engineered-clostridial LL1660 result (PMID36286488) removes both PPi-pfk and introduced TAL, limiting claims of universal necessity; the alternative C6↔C5 route remains unresolved. That result does not refute the E. coli ATP bypass assays. [MetaCyc:PWY-8178; MetaCyc:RXN-21730; PMID:31871051; PMID:36286488] PfkA annotation supports Mg dependence, homotetramer and cytoplasmic location. Canonical F6P-dependent activity is inhibited by PEP and activated by ADP/GDP; F6P has a cooperative substrate response whereas ATP does not in the cited native context. These signs, the >90% contribution to wild-type canonical PFK activity, pH effects and in-vitro reverse activity are not direct measurements of S7P regulation or whole-pathway flux. S7P turnover and F6P turnover are separate substrate contexts. [EcoCyc:6PFK-1-CPX; EcoCyc:6PFRUCTPHOS-ENZRXN; EcoCyc:REG0-7473; EcoCyc:REG0-7474; EcoCyc:REG0-7475; EcoCyc:REG0-7476; UniProtKB:P0A796] FbaA is a cytosolic class-II metal-dependent dimer. Native location/GO annotation is independent of SUBUNIT text. Two Zn sites per subunit (catalytic and structural) in the current annotation differ from the older PMID8436219 abstract's two Zn per dimer. The 2011 study (PMID22014167;2012 issue) separates untagged MG1655/pLEM1/pWKS30 material≥70% pure from pLEM5/pET28b His 6 WT and site mutants≥95% pure. As-purified metal content was up to 0.3 Zn/0.2 Ni per monomer; denaturation-assisted Zn loading produced2.3 Zn per monomer and 3.8-fold higher activity. Source numbering follows removed initiating methionine: His 110/226/264 catalytic ligands and Asp144/Glu174/Glu181 secondary-site ligands; historical His 108/111 is not silently renumbered. Native Co/Fe/Mn active metalloprotein alternatives are distinct from additive metal effects. Ni inhibits, Cu2+ strongly inhibits in vitro, low Zn slightly activates/high Zn slightly inhibits, Co slightly activates, and Ca/Mg/Mn had no effect in the measured preparation. Cytoplasmic copper is mainly cuprous, limiting physiological Cu2+ claims. Native K/ammonium activation cites personal communication in 1996; Ni/EDTA effects and earlier Crookes preparations remain source qualified. [EcoCyc:F16ALDOLASE-ENZRXN-CLASSII; EcoCyc:FRUCBISALD-CLASSII; EcoCyc:FRUCTBISALD-CLASSII-MONOMER; EcoCyc:REG0-12167; EcoCyc:REG0-12168; EcoCyc:REG0-12169; EcoCyc:REG0-8470; PMID:22014167; PMID:6996735; PMID:8436219; UniProtKB:P0AB71] In PMID22014167, untagged FbaA 20 nM challenged with Ni 16 µM is protected by His 100 µM (about 20% loss instead of 70%); GSH 1 mM enhances Ni inhibition. These are conditional activity effects relative to Ni-only challenge, not generic ligand activation/inhibition or direct FbaA binding. The rcnA/gshA comparisons and D 144A/E174A resistance support contributions of cellular ligands and the secondary metal site without uniquely proving a Ni-delivery mechanism. Source-native His/GSH formula, charge and InChI ground selected reference chemical identities, while the assay ionic form remains unstated; inconsistent native CML SMILES is retained as a conflict. MG1655 growth inhibition at 8 µM Ni depends on carbon source (glucose/fructose versus glycerol/lactate/succinate), is bacteriostatic, and FbaA activity recovers after Ni removal even with translation inhibited. Active versus passive repair remains unresolved. [PMID:22014167] UniProt FUNCTION text names GAP+E4P for SBP cleavage whereas its structured reaction and the 2009 direct assay support DHAP+E4P. Abstract-level PMID7872790 supports carbonyl substrate forms, Zn-dependent enediol(ate)-DHAP chemistry and pH effects; Cd replacement structures (PMID12595741) do not prove a physiological Cd cofactor or inhibition. Earlier phosphate-associated labeling (PMID3281666) and the later +76-Da mercaptoethanol adduct at source Cys36 (PMID7851430) concern different preparations; the latter ruled out phosphorylation and found no significant activity effect. Later phosphoproteome annotation (PMID35636362) does not reconcile these as a single constitutively modified active chain. Synthetic N-sulfonyl hydroxamate phosphate inhibitors and weaker phosphonate isosteres (PMID16236509) are bounded canonical-FBP context without an invented exact inhibitor identity. [EcoCyc:FRUCBISALD-CLASSII; PMID:12595741; PMID:16236509; PMID:19756045; PMID:3281666; PMID:35636362; PMID:7851430; PMID:7872790; UniProtKB:P0AB71] PMID31464375 uses His-tagged ASKA proteins (>90% purity;0.1 mM IPTG, 16 h at 37 °C, TALON purification). The 2019 NMR assay (15 µM monomer equivalent, 200 µM metabolites, 298 K; RF threshold0.1805/FPR5%) lists eleven FbaA binders:3PG, 6PG, AMP, ATP, citrate, GTP, malonate, NADP, PEP, PRPP and phenylpyruvate; six PfkA binders are AMP, CTP, FAD, FBP, GTP and NAD. These observations have no assigned causal sign merely from binding. The 2016 NMR paper PMID27065204 remains abstract/native scope; different buffers and thresholds limit direct comparison of binder sets. [PMID:27065204; PMID:31464375] The 2019 direct FbaA assay uses canonical FBP 1 mM, Tris10 mM pH7.5/Mg 1 mM at 30 °C,≈1 µM enzyme monomer equivalent, modifiers5 mM (hypoxanthine3.22 mM), triplicate activities and quadruplicate mixture-specific MS calibration. ATP, 3PG and PEP activate; hypoxanthine and IMP have no effect. MS combines same-mass DHAP/GAP signals. ATP is within the cited physiological range, whereas 3PG/PEP are above it. The source reports prior3PG inhibition, while the 1995 abstract PMID7872790 reports no effect from glycolytic intermediates/ATP. These source/assay-specific outcomes remain separate, and the appendix's generic inhibitor caption does not reverse measured activation. None directly measures SBP cleavage regulation. [PMID:31464375; PMID:7872790] Cra/FruR native PC00061 is a tetramer; the 1994 pT7-5 six-His assembly/ace-operator preparation (PMID8195118) differs from 1996 six-His binding-site/pfkA work (PMID8858581). Native pfkA regulatory records share siteBS785, and epd promoter records share BS264; epd-pgk-fbaA operon membership carries the fbaA expression interpretation. Cra-CPLX127 includes a native beta-D-fructofuranose1P component without a supplied ligand coefficient. Generic F1P assay identity is not assigned the native beta anomer. The 2018 abstract PMID29923648 reports F1P-dependent impairment of Cra DNA binding and negative FBP binding/effect tests, contrasting older FBP-effector discussion and the contaminant explanation in PMID30019355. Full2018 methods were unavailable. The 2021 Cra Asn50 cleavage/NTD behavior (PMID34666048) is a later preparation context, not proof that earlier specimens were cleaved. [EcoCyc:CPLX-127; EcoCyc:D-fructofuranose-1-phosphate; EcoCyc:FRU1P; EcoCyc:PC00061; EcoCyc:PD00521; EcoCyc:REG0-15081; EcoCyc:REG0-15233; EcoCyc:REG0-4838; EcoCyc:REG0-5630; PMID:19838295; PMID:29923648; PMID:30019355; PMID:34666048; PMID:8195118; PMID:8577250; PMID:8858581] Native CRP-cAMP CPLX0-226 contains CRP dimerPC00004 and cAMP; PC00004 has two P0ACJ8 chains, but ligand stoichiometry is not supplied. Positive epd-pgk-fbaA regulation is limited by the 1998 PMID9851989 abstract: deleting the CRP site had little effect under glucose whereas crp/cya loss strongly reduced epd/gapB P0, supporting an indirect response. PtsG-encoded IICBGlc contributes to glucose stimulation of that promoter. It is distinct from crr/EIIAGlc, does not establish a direct fbaA operator and is not a pathway-specific S7P transporter. [EcoCyc:CAMP; EcoCyc:CPLX0-226; EcoCyc:PC00004; EcoCyc:PD00257; EcoCyc:REG0-15234; EcoCyc:REG0-5629; Entrez:945295; Entrez:945651; PMID:9851989; UniProtKB:P0A9A9; UniProtKB:P0A9E5; UniProtKB:P13445; UniProtKB:P69783; UniProtKB:P69786; UniProtKB:P69913] PMID19838295 compares JM101-derived PB11/PB12 ΔptsH ptsI crr backgrounds and rpoS derivatives under aerobic M9 glucose conditions, distinct from BW25113 talAB. Its pET28b+/ER2566 His-RpoS or His-RpoD combined with commercial RNAP core at core:sigma1:5 supports direct transcription of the first pfkA promoter. A sigma chain is not an autonomous polymerase. fbaA expression is condition-specific and can be operon-mediated; no immediate fbaA promoter was found in the tested analysis, which is not general promoter absence. Original MG1665 and pykA/pfkA-label discrepancies remain source errors rather than reference-strain reassignments. PMID16102000 abstract describes epd-pgk-fbaA cotranscription, RNaseE cleavage and segment stability without a uniquely determined signed RNaseE effect on FbaA catalysis. [PMID:16102000; PMID:19838295] The csrA51 hypomorph in M9 glucose has reduced PfkA expression and partial growth/stress rescue after PfkA restoration (PMID26833659 plus native annotation). This is positive expression context, not a clean csrA deletion or a mapped direct RNA-binding site. Acid-associated pfkA response under aerobic but not microaerobic conditions is retained at abstract/native scope (PMID23274360), without assigning an unmeasured PhoB binding mechanism. [EcoCyc:6PFK-1-CPX; EcoCyc:TU0-45239; Entrez:947176; PMID:23274360; PMID:26833659] PMID21272324 uses BW25113 Keio cyoA(JW0422), cydB(JW0723), fnr(sourceJW1318) and fur(JW0669) deletions in continuous aerobic culture (D 0.2 h−1, 37 °C, pH7, DO35–40%; C/N 1.68 or8.42). RT-PCR, with source controls, reports increased pfkA expression in the relevant deletion comparisons, amid broad network changes. Negative reference-associated effects are therefore qualified indirect knockout inferences, not direct pfkA binding. The source Fnr gene contrast under oxygen does not identify a purified anaerobic [4Fe-4S] active species, and CyoA/CydB reference chains do not autonomously reproduce their respiratory complexes. Exact subject-reference genes and the pfkA object gene are separately grounded. [Entrez:945295; Entrez:945651; Entrez:945908; PMID:21272324; UniProtKB:P0ABJ1; UniProtKB:P0ABK2] Frozen PathBank memberPW002098.owl/rootSMP0002110 attaches Pentose PhosphateSMP0121065 (S7P-input/E4P-output context) and Glycolysis and Pyruvate DehydrogenaseSMP0000807 (DHAP-output context). Their generic Interaction markers are unsigned structural membership, not transport or inhibition. Exact local compounds remain separate from Rhea: neutral S7P/E4P and a DHAP dilithium salt C3H5Li2O6P are not merged into anions. The frozen neutral ATP/ADP/SBP forms and erroneous PfkB inclusion are explicit source conflicts. The original wholeZIP/member/root provenance is retained, with no live per-pathway download claim. [PathBank:SMP0002110] The Calvin-cycle and riboneogenesis condensation E4P+DHAP->SBP and subsequent SBP hydrolysis have different direction and energy chemistry. Classical PPP transaldolase uses S7P+GAP, while ADP-heptose formation isomerizes S7P. The ATP-dependent phosphorylation/cleavage pair is distinct from those routes and from the six-event PPi branch; shared metabolites and earlier research mentions do not merge the pathway definitions. Native PfkA sequence-based NAD-kinase prediction, antisense/production engineering, altered carbon-catabolite repression and enzyme allostery studies are neighboring enzyme contexts, not additional bypass reactions. FbaA ts8/h8, RNA/engineered substrate variants and broader physiological annotations likewise do not demonstrate more steps in this pathway. Physical substrate channeling discussed speculatively in older work is not a demonstrated multienzyme complex. Older unavailable primary bodies remain explicitly abstract/native-annotation evidence. [EcoCyc:6PFK-1-CPX; EcoCyc:FRUCBISALD-CLASSII; PMID:7872790]

Pathway type

carbohydrate metabolism

Organism scope

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Pathway network

82 nodes · 67 asserted directed edges

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli `NCBITaxon:562`	taxon
Escherichia coli K-12 `NCBITaxon:83333`	taxon
Escherichia coli str. K-12 substr. MG1655 `NCBITaxon:511145`	taxon
Escherichia coli BW25113 `NCBITaxon:679895`	taxon
sedoheptulose 7-phosphate(2-) `CHEBI:57483`	small molecule
ATP(4-) `CHEBI:30616`	small molecule
sedoheptulose 1,7-bisphosphate(4-) `CHEBI:58335`	small molecule
ADP(3-) `CHEBI:456216`	small molecule
hydron `CHEBI:15378`	small molecule
D-erythrose 4-phosphate(2-) `CHEBI:16897`	small molecule
glycerone phosphate(2-) `CHEBI:57642`	small molecule
magnesium(2+) `CHEBI:18420`	cofactor
zinc(2+) `CHEBI:29105`	cofactor
cobalt(2+) `CHEBI:48828`	cofactor
iron(2+) `CHEBI:29033`	cofactor
manganese(2+) `CHEBI:29035`	cofactor
nickel(2+) `CHEBI:49786`	small molecule
copper(2+) `CHEBI:29036`	small molecule
calcium(2+) `CHEBI:29108`	small molecule
potassium(1+) `CHEBI:29103`	small molecule
ammonium `CHEBI:28938`	small molecule
EDTA(2-) `CHEBI:64755`	small molecule
L-histidine zwitterion `CHEBI:57595`	small molecule
glutathionate(1-) `CHEBI:57925`	small molecule
3-phosphonato-D-glycerate(3-) `CHEBI:58272`	small molecule
phosphonatoenolpyruvate `CHEBI:58702`	small molecule
GDP(3-) `CHEBI:58189`	small molecule
3',5'-cyclic AMP(1-) `CHEBI:58165`	small molecule
D-fructofuranose 1-phosphate(2-) `CHEBI:58674`	small molecule
beta-D-fructofuranose 1-phosphate(2-) `CHEBI:138881`	small molecule
D-fructofuranose 1,6-bisphosphate(4-) `CHEBI:49299`	small molecule
ATP-dependent 6-phosphofructokinase isozyme 1 `UniProtKB:P0A796`	protein
Fructose-bisphosphate aldolase class 2 `UniProtKB:P0AB71`	protein
Catabolite repressor/activator `UniProtKB:P0ACP1`	protein
DNA-binding transcriptional dual regulator CRP `UniProtKB:P0ACJ8`	protein
RNA polymerase sigma factor RpoS `UniProtKB:P13445`	protein
RNA polymerase sigma factor RpoD `UniProtKB:P00579`	protein
Carbon storage regulator `UniProtKB:P69913`	protein
PTS system glucose-specific EIICB component `UniProtKB:P69786`	protein
Fumarate and nitrate reduction regulatory protein `UniProtKB:P0A9E5`	protein
Ferric uptake regulation protein `UniProtKB:P0A9A9`	protein
Cytochrome bo(3) ubiquinol oxidase subunit 2 `UniProtKB:P0ABJ1`	protein
Cytochrome bd-I ubiquinol oxidase subunit 2 `UniProtKB:P0ABK2`	protein
6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	complex
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	complex
DNA-binding transcriptional dual regulator Cra `EcoCyc:PC00061`	complex
Cra-β-D-fructofuranose 1-phosphate `EcoCyc:CPLX-127`	complex
DNA-binding transcriptional dual regulator CRP `EcoCyc:PC00004`	complex
CRP-cyclic-AMP DNA-binding transcriptional dual regulator `EcoCyc:CPLX0-226`	complex
pfkA `Entrez:948412`	gene
fbaA `Entrez:947415`	gene
cytoplasm `GO:0005737`	cellular component
cytosol `GO:0005829`	cellular component
D-Sedoheptulose 7-phosphate `PathBank:SMP0002110/Compound/PW_C000843`	small molecule
D-Erythrose 4-phosphate `PathBank:SMP0002110/Compound/PW_C001019`	small molecule
Glycerone phosphate `PathBank:SMP0002110/Compound/PW_C042631`	small molecule
beta-D-fructofuranose 6-phosphate(2-) `CHEBI:57634`	small molecule
D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	molecular activity	left to right
D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	molecular activity	right to left
Pentose Phosphate `PathBank:SMP0121065`	pathway
Glycolysis and Pyruvate Dehydrogenase `PathBank:SMP0000807`	pathway

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	part_of The exact native reaction-list includes RXN0-6541. The ATP-dependent bypass has two internal events; neighboring PPP and glycolysis links are interfaces.	`MetaCyc:PWY0-1517`	MetaCyc:PWY0-1517 Source assertion: The exact native reaction-list includes RXN0-6541. The ATP-dependent bypass has two internal events; neighboring PPP and glycolysis links are interfaces. Source location `XPath /ptools-xml/Pathway/reaction-list/Reaction[@frameid="RXN0-6541"]`
D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	part_of The exact native reaction-list includes SEDOBISALDOL-RXN. The ATP-dependent bypass has two internal events; neighboring PPP and glycolysis links are interfaces.	`MetaCyc:PWY0-1517`	MetaCyc:PWY0-1517 Source assertion: The exact native reaction-list includes SEDOBISALDOL-RXN. The ATP-dependent bypass has two internal events; neighboring PPP and glycolysis links are interfaces. Source location `XPath /ptools-xml/Pathway/reaction-list/Reaction[@frameid="SEDOBISALDOL-RXN"]`
sedoheptulose 7-phosphate(2-) `CHEBI:57483`	consumes RHEA:31444 substrates contains CHEBI:57483 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	RHEA:31444 Source assertion: RHEA:31444 substrates contains CHEBI:57483 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:31444 rh:substrates; http://rdf.rhea-db.org/Participant_31443_compound_3830 rh:compound http://rdf.rhea-db.org/Compound_3830; rh:contains1`
ATP(4-) `CHEBI:30616`	consumes RHEA:31444 substrates contains CHEBI:30616 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	RHEA:31444 Source assertion: RHEA:31444 substrates contains CHEBI:30616 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:31444 rh:substrates; http://rdf.rhea-db.org/Participant_31443_compound_6372 rh:compound http://rdf.rhea-db.org/Compound_6372; rh:contains1`
D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	produces RHEA:31444 products contains CHEBI:58335 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	sedoheptulose 1,7-bisphosphate(4-) `CHEBI:58335`	RHEA:31444 Source assertion: RHEA:31444 products contains CHEBI:58335 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:31444 rh:products; http://rdf.rhea-db.org/Participant_31443_compound_2479 rh:compound http://rdf.rhea-db.org/Compound_2479; rh:contains1`
D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	produces RHEA:31444 products contains CHEBI:456216 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	ADP(3-) `CHEBI:456216`	RHEA:31444 Source assertion: RHEA:31444 products contains CHEBI:456216 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:31444 rh:products; http://rdf.rhea-db.org/Participant_31443_compound_2710 rh:compound http://rdf.rhea-db.org/Compound_2710; rh:contains1`
D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	produces RHEA:31444 products contains CHEBI:15378 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	hydron `CHEBI:15378`	RHEA:31444 Source assertion: RHEA:31444 products contains CHEBI:15378 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:31444 rh:products; http://rdf.rhea-db.org/Participant_31443_compound_3249 rh:compound http://rdf.rhea-db.org/Compound_3249; rh:contains1`
sedoheptulose 1,7-bisphosphate(4-) `CHEBI:58335`	consumes RHEA:30169 substrates contains CHEBI:58335 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	RHEA:30169 Source assertion: RHEA:30169 substrates contains CHEBI:58335 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:30169 rh:substrates; http://rdf.rhea-db.org/Participant_30167_compound_2479 rh:compound http://rdf.rhea-db.org/Compound_2479; rh:contains1`
D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	produces RHEA:30169 products contains CHEBI:16897 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	D-erythrose 4-phosphate(2-) `CHEBI:16897`	RHEA:30169 Source assertion: RHEA:30169 products contains CHEBI:16897 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:30169 rh:products; http://rdf.rhea-db.org/Participant_30167_compound_5282 rh:compound http://rdf.rhea-db.org/Compound_5282; rh:contains1`
D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	produces RHEA:30169 products contains CHEBI:57642 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child.	glycerone phosphate(2-) `CHEBI:57642`	RHEA:30169 Source assertion: RHEA:30169 products contains CHEBI:57642 at coefficient 1. Exact native directional participants and containsN multiplicity define this side; generic S7P is not replaced by an alpha-pyranose child. Source location `RHEA:30169 rh:products; http://rdf.rhea-db.org/Participant_30167_compound_4255 rh:compound http://rdf.rhea-db.org/Compound_4255; rh:contains1`
D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	provides_input_for The native ordering links S7P phosphorylation to SBP cleavage through shared SBP. This direct intermediate relation adds no TPI, transport or PPi-dependent event.	D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	MetaCyc:PWY0-1517 Source assertion: The native ordering links S7P phosphorylation to SBP cleavage through shared SBP. This direct intermediate relation adds no TPI, transport or PPi-dependent event. Source location `XPath /ptools-xml/Pathway/reaction-ordering`
6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	catalyzes The exact native enzyme slot identifies this catalytic assembly for the SBP-bypass activity. Attached direct-assay annotation cites PMID19756045; this reference mapping does not assert ordinary wild-type whole-pathway flux.	D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	EcoCyc:ENZRXN0-7407 Source assertion: The exact native enzyme slot identifies this catalytic assembly for the SBP-bypass activity. Attached direct-assay annotation cites PMID19756045; this reference mapping does not assert ordinary wild-type whole-pathway flux. Source location `XPath /ptools-xml/Enzymatic-Reaction/enzyme \| /ptools-xml/Enzymatic-Reaction/reaction`
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	catalyzes The exact native enzyme slot identifies this catalytic assembly for the SBP-bypass activity. Attached direct-assay annotation cites PMID19756045; this reference mapping does not assert ordinary wild-type whole-pathway flux.	D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	EcoCyc:ENZRXN0-7406 Source assertion: The exact native enzyme slot identifies this catalytic assembly for the SBP-bypass activity. Attached direct-assay annotation cites PMID19756045; this reference mapping does not assert ordinary wild-type whole-pathway flux. Source location `XPath /ptools-xml/Enzymatic-Reaction/enzyme \| /ptools-xml/Enzymatic-Reaction/reaction`
6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	has_part The direct native component specifies 4 copies of 6PFK-1-MONOMER. Reference-chain membership does not imply that an isolated monomer performs the complete reaction.	ATP-dependent 6-phosphofructokinase isozyme 1 `UniProtKB:P0A796`	EcoCyc:6PFK-1-CPX Source assertion: The direct native component specifies 4 copies of 6PFK-1-MONOMER. Reference-chain membership does not imply that an isolated monomer performs the complete reaction. Source location `XPath /ptools-xml/Protein/component` EcoCyc:6PFK-1-MONOMER Source assertion: The monomer unification cross-reference identifies UniProtKB:P0A796. It does not prove sequence equality of each historical or tagged assay preparation. Source location `XPath /ptools-xml/Protein/dblink[dblink-db="UNIPROT" and dblink-oid="P0A796"]` UniProtKB:P0A796 Source assertion: The reviewed native annotation supports the homotetramer. Source location `entry[primaryAccession='P0A796'].comments[commentType='SUBUNIT']`
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	has_part The direct native component specifies 2 copies of FRUCTBISALD-CLASSII-MONOMER. Reference-chain membership does not imply that an isolated monomer performs the complete reaction.	Fructose-bisphosphate aldolase class 2 `UniProtKB:P0AB71`	EcoCyc:FRUCBISALD-CLASSII Source assertion: The direct native component specifies 2 copies of FRUCTBISALD-CLASSII-MONOMER. Reference-chain membership does not imply that an isolated monomer performs the complete reaction. Source location `XPath /ptools-xml/Protein/component` EcoCyc:FRUCTBISALD-CLASSII-MONOMER Source assertion: The monomer unification cross-reference identifies UniProtKB:P0AB71. It does not prove sequence equality of each historical or tagged assay preparation. Source location `XPath /ptools-xml/Protein/dblink[dblink-db="UNIPROT" and dblink-oid="P0AB71"]` UniProtKB:P0AB71 Source assertion: The reviewed native annotation supports the homodimer. Source location `entry[primaryAccession='P0AB71'].comments[commentType='SUBUNIT']`
6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX` experimental construct: 2009 six-His ASKA PfkA preparation; assay clone is not asserted sequence-equal to MG1655 P0A796. 2 µM enzyme, S7P 5 mM, ATP 2 mM, potassium MOPS 50 mM, 37 °C, 1 h, n=5. This differs from the 2020 pET-28b/Rosetta preparation. Qualification evidence PMID:19756045 Source assertion: Methods specify purified six-His ASKA PfkA/FbaA, substrates and enzyme concentrations, ATP, potassium MOPS and the one-hour assay. Source location `XPath /article/body/sec[4]/sec[11]/p[1] \| /article/body/sec[4]/sec[11]/p[2]`	catalyzes PfkA with S7P and ATP produces candidate SBP; FbaA-only and no-enzyme controls do not. SBP was quantified with F1,6BP calibration because no authentic standard was available.	D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	PMID:19756045 Source assertion: PfkA with S7P and ATP produces candidate SBP; FbaA-only and no-enzyme controls do not. SBP was quantified with F1,6BP calibration because no authentic standard was available. Source location `XPath /article/body/sec[2]/sec[6]/table-wrap \| /article/body/sec[2]/sec[4]/p[1] \| /article/body/sec[4]/sec[11]/p[2]` PMID:19756045 Source assertion: The primary combined-enzyme assay identifies the two-step route. Results use m/z369.0 while Methods use367.0; the internal discrepancy remains explicit. Source location `XPath /article/body/sec[2]/sec[6]/p \| /article/body/sec[4]/sec[11]/p[2]`
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2009 six-His ASKA FbaA, 2 µM, assayed with PfkA-generated SBP from S7P 5 mM and ATP 2 mM in potassium MOPS, 37 °C, 1 h, n=5. This is not an isolated native monomer or an authenticated SBP-standard assay. Qualification evidence PMID:19756045 Source assertion: The primary methods specify the ASKA tagged preparations and conditions for the combined PfkA/FbaA assay. Source location `XPath /article/body/sec[4]/sec[11]/p[1] \| /article/body/sec[4]/sec[11]/p[2]`	catalyzes Direct two-enzyme evidence supports SBP cleavage to E4P and DHAP. The no-enzyme, PfkA-only, FbaA-only and F6P comparisons remain distinct; the model supplement and UniProt FUNCTION GAP wording do not replace measured DHAP.	D-sedoheptulose 1,7-bisphosphate => D-erythrose 4-phosphate + dihydroxyacetone phosphate `RHEA:30169`	PMID:19756045 Source assertion: Adding FbaA to PfkA/S7P/ATP yields measured E4P and DHAP; PfkA alone yields candidate SBP without those products. The five separate controls constrain the interpretation. Source location `XPath /article/body/sec[2]/sec[6]/table-wrap`
6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX` experimental construct: 2020 BW25113_3916 PfkA in pET-28b(+), DH5α cloning and Rosetta His-affinity expression. Coupled55 °C assay uses S7P Ba salt, Mg5 mM, ATP2 mM, ADP0.25 mM and rabbit aldolase/G3PDH/NADH; no added TPI. Distinct from F6P/2009 assays. Qualification evidence PMID:31871051 Source assertion: The primary methods identify E. coli PfkA cloning, pET-28b expression, His-affinity preparation and coupled kinase conditions; S7P is supplied as its Ba salt. Source location `XPath /article/body/sec[5]/sec[3]/p[1] \| /article/body/sec[5]/sec[3]/p[3] \| /article/body/sec[5]/sec[7]/p[2] \| /article/body/sec[5]/sec[7]/p[1]`	catalyzes Independent 2020 S7P kinase capacity under a 55 °C coupled assay. Coupling enzymes, NADH and suspected trace TPI are detection context, not new pathway events. Thesis Figure S4 presents both Michaelis–Menten and Hill fits; neither establishes physiological cooperativity of bypass flux.	D-sedoheptulose 7-phosphate + ATP => D-sedoheptulose 1,7-bisphosphate + ADP + H(+) `RHEA:31444`	PMID:31871051 Source assertion: The E. coli PfkA S7P comparison reports apparent Km2.5 mM and kcat0.25 s−1, versus F6P0.065 mM and1.2 s−1; the S7P catalytic-efficiency entry is retained as reported, not recalculated. Source location `XPath /article/body/sec[2]/sec[2]/table-wrap \| /article/body/sec[2]/sec[2]/p[5]`
ATP-dependent 6-phosphofructokinase isozyme 1 `UniProtKB:P0A796`	located_in The issuing reference protein annotation places PfkA in the cytoplasm, retaining the annotation evidence role rather than claiming a new experiment.	cytoplasm `GO:0005737`	UniProtKB:P0A796 Source assertion: The issuing reference protein annotation places PfkA in the cytoplasm, retaining the annotation evidence role rather than claiming a new experiment. Source location `entry[primaryAccession='P0A796'].comments[commentType='SUBCELLULAR LOCATION']`
Fructose-bisphosphate aldolase class 2 `UniProtKB:P0AB71`	located_in The exact cytosol GO annotation supplies IDA evidence and its cited localization studies. Location is not inferred from the protein SUBUNIT field.	cytosol `GO:0005829`	EcoCyc:FRUCTBISALD-CLASSII-MONOMER Source assertion: The exact cytosol GO annotation supplies IDA evidence and its cited localization studies. Location is not inferred from the protein SUBUNIT field. Source location `XPath /ptools-xml/Protein/has-go-term[GO-Term[@frameid="GO:0005829"]]`
6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	has_cofactor The reviewed reference annotation supports Mg2+ dependence, separate from ATP as a consumed core cosubstrate. The 2020 assay includes Mg but does not titrate an S7P-specific requirement.	magnesium(2+) `CHEBI:18420`	UniProtKB:P0A796 Source assertion: The reviewed reference annotation supports Mg2+ dependence, separate from ATP as a consumed core cosubstrate. The 2020 assay includes Mg but does not titrate an S7P-specific requirement. Source location `entry[primaryAccession='P0A796'].comments[commentType='COFACTOR']`
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	has_cofactor Class-II Zn dependence; the old per-dimer estimate and newer two-sites-per-subunit annotation differ. 2011 as-purified and Zn-loaded occupancies remain construct-specific context, not a universal fixed loading.	zinc(2+) `CHEBI:29105`	UniProtKB:P0AB71 Source assertion: The issuing annotation gives catalytic and structural Zn sites, two Zn per subunit. Site capacity is not equal to solution occupancy in every purified preparation. Source location `entry[primaryAccession='P0AB71'].comments[commentType='COFACTOR']` PMID:8436219 Source assertion: The older abstract reports two Zn per enzyme dimer; this is retained as a preparation/source discrepancy, not silently changed to the newer per-subunit capacity. Source location `resultList.result[id='8436219'].abstractText`
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	has_cofactor Alternative Co2+-containing FbaA activity is source-qualified. The 2011 assay found no effect of added Mn on its preparation; alternative cofactor substitution and additive activation are different experiments.	cobalt(2+) `CHEBI:48828`	EcoCyc:FRUCBISALD-CLASSII Source assertion: The native annotation reports active Co2+ metalloprotein alternatives to Zn. This is older biochemical annotation, not a claim that adding this ion stimulates every holoenzyme preparation. Source location `XPath /ptools-xml/Protein/comment`
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	has_cofactor Alternative Fe2+-containing FbaA activity is source-qualified. The 2011 assay found no effect of added Mn on its preparation; alternative cofactor substitution and additive activation are different experiments.	iron(2+) `CHEBI:29033`	EcoCyc:FRUCBISALD-CLASSII Source assertion: The native annotation reports active Fe2+ metalloprotein alternatives to Zn. This is older biochemical annotation, not a claim that adding this ion stimulates every holoenzyme preparation. Source location `XPath /ptools-xml/Protein/comment`
fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	has_cofactor Alternative Mn2+-containing FbaA activity is source-qualified. The 2011 assay found no effect of added Mn on its preparation; alternative cofactor substitution and additive activation are different experiments.	manganese(2+) `CHEBI:29035`	EcoCyc:FRUCBISALD-CLASSII Source assertion: The native annotation reports active Mn2+ metalloprotein alternatives to Zn. This is older biochemical annotation, not a claim that adding this ion stimulates every holoenzyme preparation. Source location `XPath /ptools-xml/Protein/comment`
phosphonatoenolpyruvate `CHEBI:58702`	inhibits PEP regulation is established for canonical F6P-dependent PfkA activity. Transfer of its sign or magnitude to the ATP-dependent S7P bypass has not been directly demonstrated by these sources.	6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	EcoCyc:REG0-7473 Source assertion: The native regulation assigns PEP a negative effect on 6PFRUCTPHOS-ENZRXN, the canonical F6P reaction. This is not a directly measured effect on S7P turnover. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/regulated-entity \| /ptools-xml/Regulation/mode` UniProtKB:P0A796 Source assertion: The reviewed reference annotation reports allosteric PEP inhibition and ADP/GDP activation of phosphofructokinase; source reaction scope is retained. Source location `entry[primaryAccession='P0A796'].comments[commentType='ACTIVITY REGULATION']`
ADP(3-) `CHEBI:456216`	activates ADP regulation is established for canonical F6P-dependent PfkA activity. Transfer of its sign or magnitude to the ATP-dependent S7P bypass has not been directly demonstrated by these sources.	6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	EcoCyc:REG0-7474 Source assertion: The native regulation assigns ADP a positive effect on 6PFRUCTPHOS-ENZRXN, the canonical F6P reaction. This is not a directly measured effect on S7P turnover. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/regulated-entity \| /ptools-xml/Regulation/mode` UniProtKB:P0A796 Source assertion: The reviewed reference annotation reports allosteric PEP inhibition and ADP/GDP activation of phosphofructokinase; source reaction scope is retained. Source location `entry[primaryAccession='P0A796'].comments[commentType='ACTIVITY REGULATION']`
GDP(3-) `CHEBI:58189`	activates GDP regulation is established for canonical F6P-dependent PfkA activity. Transfer of its sign or magnitude to the ATP-dependent S7P bypass has not been directly demonstrated by these sources.	6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	EcoCyc:REG0-7475 Source assertion: The native regulation assigns GDP a positive effect on 6PFRUCTPHOS-ENZRXN, the canonical F6P reaction. This is not a directly measured effect on S7P turnover. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/regulated-entity \| /ptools-xml/Regulation/mode` UniProtKB:P0A796 Source assertion: The reviewed reference annotation reports allosteric PEP inhibition and ADP/GDP activation of phosphofructokinase; source reaction scope is retained. Source location `entry[primaryAccession='P0A796'].comments[commentType='ACTIVITY REGULATION']`
ammonium `CHEBI:28938`	activates Native canonical-activity ammonium effect. K+/ammonium evidence is an explicit personal-communication annotation; EDTA charge identity is the native source link. The unspecified reagent form and older Crookes preparation context are not silently converted into a new direct assay.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	EcoCyc:REG0-12168 Source assertion: The native regulation assigns ammonium a positive effect on F16ALDOLASE-ENZRXN-CLASSII. It concerns canonical FBP cleavage, not a measured SBP-turnover response. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/regulated-entity \| /ptools-xml/Regulation/mode` EcoCyc:F16ALDOLASE-ENZRXN-CLASSII Source assertion: The native enzyme comment supplies assay/annotation context; K and ammonium activation is attributed to personal communication cited in1996. Older biochemical preparations are not automatically the current MG1655 reference. Source location `XPath /ptools-xml/Enzymatic-Reaction/comment`
potassium(1+) `CHEBI:29103`	activates Native canonical-activity potassium effect. K+/ammonium evidence is an explicit personal-communication annotation; EDTA charge identity is the native source link. The unspecified reagent form and older Crookes preparation context are not silently converted into a new direct assay.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	EcoCyc:REG0-12169 Source assertion: The native regulation assigns potassium a positive effect on F16ALDOLASE-ENZRXN-CLASSII. It concerns canonical FBP cleavage, not a measured SBP-turnover response. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/regulated-entity \| /ptools-xml/Regulation/mode` EcoCyc:F16ALDOLASE-ENZRXN-CLASSII Source assertion: The native enzyme comment supplies assay/annotation context; K and ammonium activation is attributed to personal communication cited in1996. Older biochemical preparations are not automatically the current MG1655 reference. Source location `XPath /ptools-xml/Enzymatic-Reaction/comment`
EDTA(2-) `CHEBI:64755`	inhibits Native canonical-activity EDTA effect. K+/ammonium evidence is an explicit personal-communication annotation; EDTA charge identity is the native source link. The unspecified reagent form and older Crookes preparation context are not silently converted into a new direct assay.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII`	EcoCyc:REG0-8470 Source assertion: The native regulation assigns EDTA a negative effect on F16ALDOLASE-ENZRXN-CLASSII. It concerns canonical FBP cleavage, not a measured SBP-turnover response. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/regulated-entity \| /ptools-xml/Regulation/mode` EcoCyc:F16ALDOLASE-ENZRXN-CLASSII Source assertion: The native enzyme comment supplies assay/annotation context; K and ammonium activation is attributed to personal communication cited in1996. Older biochemical preparations are not automatically the current MG1655 reference. Source location `XPath /ptools-xml/Enzymatic-Reaction/comment`
nickel(2+) `CHEBI:49786`	inhibits Time- and concentration-dependent inhibition; Zn-site substitution is supported, not direct SBP kinetics. Calcium, Mg and Mn had no effect in the same comparison; those negatives do not refute activity of separately substituted metalloproteins.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 untagged FbaA purified from MG1655/pLEM1 (pWKS30), ≥70% purity; canonical FBP coupled activity. In-vitro challenge: 50 mM Tris-HCl pH7.5, aerobic25 °C. Separate pLEM5 His6 WT/mutant controls are not pooled into this preparation. Qualification evidence PMID:22014167 Source assertion: Methods distinguish untagged pLEM1 purification from His-tagged pLEM5 WT/mutants, and specify the aerobic Tris-buffer challenge assay. Source location `XPath /collection/document/passage[40] \| /collection/document/passage[50] \| /collection/document/passage[52]`	PMID:22014167 Source assertion: The primary Results/Discussion describe Ni2+ with this sign under the purified canonical FbaA assay. Time- and concentration-dependent inhibition; Zn-site substitution is supported, not direct SBP kinetics. Source location `XPath /collection/document/passage[21] \| /collection/document/passage[29]`
copper(2+) `CHEBI:29036`	inhibits Substantial inhibition in vitro; the authors caution that cytoplasmic copper is mainly cuprous, so physiological Cu2+ regulation is not established. Calcium, Mg and Mn had no effect in the same comparison; those negatives do not refute activity of separately substituted metalloproteins.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 untagged FbaA purified from MG1655/pLEM1 (pWKS30), ≥70% purity; canonical FBP coupled activity. In-vitro challenge: 50 mM Tris-HCl pH7.5, aerobic25 °C. Separate pLEM5 His6 WT/mutant controls are not pooled into this preparation. Qualification evidence PMID:22014167 Source assertion: Methods distinguish untagged pLEM1 purification from His-tagged pLEM5 WT/mutants, and specify the aerobic Tris-buffer challenge assay. Source location `XPath /collection/document/passage[40] \| /collection/document/passage[50] \| /collection/document/passage[52]`	PMID:22014167 Source assertion: The primary Results/Discussion describe Cu2+ with this sign under the purified canonical FbaA assay. Substantial inhibition in vitro; the authors caution that cytoplasmic copper is mainly cuprous, so physiological Cu2+ regulation is not established. Source location `XPath /collection/document/passage[21] \| /collection/document/passage[29]`
zinc(2+) `CHEBI:29105`	activates Slight activation at low added Zn; full loading requires the separate denaturation/metallation treatment. Calcium, Mg and Mn had no effect in the same comparison; those negatives do not refute activity of separately substituted metalloproteins.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 untagged FbaA purified from MG1655/pLEM1 (pWKS30), ≥70% purity; canonical FBP coupled activity. In-vitro challenge: 50 mM Tris-HCl pH7.5, aerobic25 °C. Separate pLEM5 His6 WT/mutant controls are not pooled into this preparation. Qualification evidence PMID:22014167 Source assertion: Methods distinguish untagged pLEM1 purification from His-tagged pLEM5 WT/mutants, and specify the aerobic Tris-buffer challenge assay. Source location `XPath /collection/document/passage[40] \| /collection/document/passage[50] \| /collection/document/passage[52]`	PMID:22014167 Source assertion: The primary Results/Discussion describe low added Zn2+ with this sign under the purified canonical FbaA assay. Slight activation at low added Zn; full loading requires the separate denaturation/metallation treatment. Source location `XPath /collection/document/passage[21] \| /collection/document/passage[29]`
zinc(2+) `CHEBI:29105`	inhibits Very slight inhibition at higher added Zn; this does not negate the essential catalytic Zn role. Calcium, Mg and Mn had no effect in the same comparison; those negatives do not refute activity of separately substituted metalloproteins.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 untagged FbaA purified from MG1655/pLEM1 (pWKS30), ≥70% purity; canonical FBP coupled activity. In-vitro challenge: 50 mM Tris-HCl pH7.5, aerobic25 °C. Separate pLEM5 His6 WT/mutant controls are not pooled into this preparation. Qualification evidence PMID:22014167 Source assertion: Methods distinguish untagged pLEM1 purification from His-tagged pLEM5 WT/mutants, and specify the aerobic Tris-buffer challenge assay. Source location `XPath /collection/document/passage[40] \| /collection/document/passage[50] \| /collection/document/passage[52]`	PMID:22014167 Source assertion: The primary Results/Discussion describe higher added Zn2+ with this sign under the purified canonical FbaA assay. Very slight inhibition at higher added Zn; this does not negate the essential catalytic Zn role. Source location `XPath /collection/document/passage[21] \| /collection/document/passage[29]`
cobalt(2+) `CHEBI:48828`	activates Slight stimulation under this preparation/assay; alternative Co metalloprotein annotations are separate evidence. Calcium, Mg and Mn had no effect in the same comparison; those negatives do not refute activity of separately substituted metalloproteins.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 untagged FbaA purified from MG1655/pLEM1 (pWKS30), ≥70% purity; canonical FBP coupled activity. In-vitro challenge: 50 mM Tris-HCl pH7.5, aerobic25 °C. Separate pLEM5 His6 WT/mutant controls are not pooled into this preparation. Qualification evidence PMID:22014167 Source assertion: Methods distinguish untagged pLEM1 purification from His-tagged pLEM5 WT/mutants, and specify the aerobic Tris-buffer challenge assay. Source location `XPath /collection/document/passage[40] \| /collection/document/passage[50] \| /collection/document/passage[52]`	PMID:22014167 Source assertion: The primary Results/Discussion describe Co2+ with this sign under the purified canonical FbaA assay. Slight stimulation under this preparation/assay; alternative Co metalloprotein annotations are separate evidence. Source location `XPath /collection/document/passage[21] \| /collection/document/passage[29]`
EDTA(2-) `CHEBI:64755`	inhibits Purification of untagged pLEM1 FbaA was confirmed by sensitivity to100 µM EDTA; this is an independent preparation-specific chelator effect.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 untagged FbaA purified from MG1655/pLEM1 (pWKS30), ≥70% purity; canonical FBP coupled activity. In-vitro challenge: 50 mM Tris-HCl pH7.5, aerobic25 °C. Separate pLEM5 His6 WT/mutant controls are not pooled into this preparation. Qualification evidence PMID:22014167 Source assertion: Methods distinguish untagged pLEM1 purification from His-tagged pLEM5 WT/mutants, and specify the aerobic Tris-buffer challenge assay. Source location `XPath /collection/document/passage[40] \| /collection/document/passage[50] \| /collection/document/passage[52]`	PMID:22014167 Source assertion: Purification of untagged pLEM1 FbaA was confirmed by sensitivity to100 µM EDTA; this is an independent preparation-specific chelator effect. Source location `XPath /collection/document/passage[50]`
L-histidine zwitterion `CHEBI:57595`	activates Conditional preservation of FbaA activity during Ni challenge. His is a Ni ligand; direct FbaA binding or an effect without Ni is not inferred. The selected physiological histidine form does not establish assay protonation state.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 as-purified untagged MG1655/pLEM1 FbaA20 nM challenged with Ni2+16 µM, with His100 µM or GSH1 mM, aerobic25 °C. Effect is relative to the Ni-only condition; no direct ligand binding to FbaA or universal modifier effect is asserted. Qualification evidence PMID:22014167 Source assertion: Figure7A uses as-purified FbaA20 nM and Ni16 µM with His100 µM or reduced glutathione1 mM; the untagged purification is described separately. Source location `XPath /collection/document/passage[50] \| /collection/document/passage[117]`	PMID:22014167 Source assertion: Histidine protects Ni-challenged FbaA: about20% activity loss versus70% without histidine. The positive sign is conditional protection against Ni, not direct activation of untreated FbaA. Source location `XPath /collection/document/passage[25] \| /collection/document/passage[117]` EcoCyc:HIS Source assertion: The native reference compound formula, charge, InChI and ChEBI link support this selected identity. Its CML SMILES is inconsistent and not used. The primary assay does not measure a unique reagent protonation state. Source location `XPath /ptools-xml/Compound/common-name \| /ptools-xml/Compound/dblink[dblink-db="CHEBI"] \| /ptools-xml/Compound/cml \| /ptools-xml/Compound/inchi`
glutathionate(1-) `CHEBI:57925`	inhibits Conditional sensitization in the Ni-containing assay, not generic glutathione inhibition of FbaA. The source specifies reduced glutathione; it does not measure the ligand protonation state or establish direct enzyme binding.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2011 as-purified untagged MG1655/pLEM1 FbaA20 nM challenged with Ni2+16 µM, with His100 µM or GSH1 mM, aerobic25 °C. Effect is relative to the Ni-only condition; no direct ligand binding to FbaA or universal modifier effect is asserted. Qualification evidence PMID:22014167 Source assertion: Figure7A uses as-purified FbaA20 nM and Ni16 µM with His100 µM or reduced glutathione1 mM; the untagged purification is described separately. Source location `XPath /collection/document/passage[50] \| /collection/document/passage[117]`	PMID:22014167 Source assertion: Reduced glutathione enhances Ni-dependent FbaA inhibition. The rcnA/gshA comparison supports a cellular contribution; the proposed delivery mechanism is not uniquely established. Source location `XPath /collection/document/passage[25] \| /collection/document/passage[117]` EcoCyc:GLUTATHIONE Source assertion: The native reference compound formula, charge, InChI and ChEBI link support this selected identity. Its CML SMILES is inconsistent and not used. The primary assay does not measure a unique reagent protonation state. Source location `XPath /ptools-xml/Compound/common-name \| /ptools-xml/Compound/dblink[dblink-db="CHEBI"] \| /ptools-xml/Compound/cml \| /ptools-xml/Compound/inchi`
ATP(4-) `CHEBI:30616`	activates ATP activates the assayed canonical FBP cleavage, not directly measured SBP cleavage. ATP concentration is within the cited physiological range;3PG/PEP concentrations exceed it. Earlier3PG inhibition and1995 no-effect reports remain separate conflicting assay contexts.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2019 ASKA His-tagged FbaA (>90% purity), TALON-purified after0.1 mM IPTG/16 h/37 °C. Canonical FBP1 mM assay at30 °C in Tris10 mM pH7.5/Mg1 mM; enzyme≈1 µM monomer equivalent and modifier5 mM; triplicate activity measurements. Qualification evidence PMID:31464375 Source assertion: Methods identify His-tagged ASKA preparations, purification, expression and the30 °C FBP activity assay; this is distinct from the2009 SBP assay and2011 untagged preparation. Source location `XPath /article/body/sec[4]/sec[2]/sec[1]/p \| /article/body/sec[4]/sec[2]/sec[6]/sec[2]/p`	PMID:31464375 Source assertion: The purified-enzyme assay reports activation by ATP. Hypoxanthine and IMP show no effect in the same assay; NMR binding alone was not used to assign these signs. Source location `XPath /article/body/sec[2]/sec[4]/p` PMID:31464375 Source assertion: The assay uses FBP1 mM and modifiers5 mM, with MS calibration for combined DHAP/GAP and triplicate activities; hypoxanthine is3.22 mM. Source location `XPath /article/body/sec[4]/sec[2]/sec[6]/sec[2]/p`
3-phosphonato-D-glycerate(3-) `CHEBI:58272`	activates 3-phosphoglycerate activates the assayed canonical FBP cleavage, not directly measured SBP cleavage. ATP concentration is within the cited physiological range;3PG/PEP concentrations exceed it. Earlier3PG inhibition and1995 no-effect reports remain separate conflicting assay contexts.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2019 ASKA His-tagged FbaA (>90% purity), TALON-purified after0.1 mM IPTG/16 h/37 °C. Canonical FBP1 mM assay at30 °C in Tris10 mM pH7.5/Mg1 mM; enzyme≈1 µM monomer equivalent and modifier5 mM; triplicate activity measurements. Qualification evidence PMID:31464375 Source assertion: Methods identify His-tagged ASKA preparations, purification, expression and the30 °C FBP activity assay; this is distinct from the2009 SBP assay and2011 untagged preparation. Source location `XPath /article/body/sec[4]/sec[2]/sec[1]/p \| /article/body/sec[4]/sec[2]/sec[6]/sec[2]/p`	PMID:31464375 Source assertion: The purified-enzyme assay reports activation by 3-phosphoglycerate. Hypoxanthine and IMP show no effect in the same assay; NMR binding alone was not used to assign these signs. Source location `XPath /article/body/sec[2]/sec[4]/p` PMID:31464375 Source assertion: The assay uses FBP1 mM and modifiers5 mM, with MS calibration for combined DHAP/GAP and triplicate activities; hypoxanthine is3.22 mM. Source location `XPath /article/body/sec[4]/sec[2]/sec[6]/sec[2]/p`
phosphonatoenolpyruvate `CHEBI:58702`	activates PEP activates the assayed canonical FBP cleavage, not directly measured SBP cleavage. ATP concentration is within the cited physiological range;3PG/PEP concentrations exceed it. Earlier3PG inhibition and1995 no-effect reports remain separate conflicting assay contexts.	fructose-bisphosphate aldolase class II `EcoCyc:FRUCBISALD-CLASSII` experimental construct: 2019 ASKA His-tagged FbaA (>90% purity), TALON-purified after0.1 mM IPTG/16 h/37 °C. Canonical FBP1 mM assay at30 °C in Tris10 mM pH7.5/Mg1 mM; enzyme≈1 µM monomer equivalent and modifier5 mM; triplicate activity measurements. Qualification evidence PMID:31464375 Source assertion: Methods identify His-tagged ASKA preparations, purification, expression and the30 °C FBP activity assay; this is distinct from the2009 SBP assay and2011 untagged preparation. Source location `XPath /article/body/sec[4]/sec[2]/sec[1]/p \| /article/body/sec[4]/sec[2]/sec[6]/sec[2]/p`	PMID:31464375 Source assertion: The purified-enzyme assay reports activation by PEP. Hypoxanthine and IMP show no effect in the same assay; NMR binding alone was not used to assign these signs. Source location `XPath /article/body/sec[2]/sec[4]/p` PMID:31464375 Source assertion: The assay uses FBP1 mM and modifiers5 mM, with MS calibration for combined DHAP/GAP and triplicate activities; hypoxanthine is3.22 mM. Source location `XPath /article/body/sec[4]/sec[2]/sec[6]/sec[2]/p`
DNA-binding transcriptional dual regulator Cra `EcoCyc:PC00061`	has_part The native component identifies 4 copies of PD00521. This supports reference assembly composition, not occupancy or sequence identity of every tagged assay preparation.	Catabolite repressor/activator `UniProtKB:P0ACP1`	EcoCyc:PC00061 Source assertion: The native component identifies 4 copies of PD00521. This supports reference assembly composition, not occupancy or sequence identity of every tagged assay preparation. Source location `XPath /ptools-xml/Protein/component` EcoCyc:PD00521 Source assertion: The exact native chain unification identifies UniProtKB:P0ACP1. Source location `XPath /ptools-xml/Protein/dblink[dblink-db="UNIPROT"]`
DNA-binding transcriptional dual regulator CRP `EcoCyc:PC00004`	has_part The native component identifies 2 copies of PD00257. This supports reference assembly composition, not occupancy or sequence identity of every tagged assay preparation.	DNA-binding transcriptional dual regulator CRP `UniProtKB:P0ACJ8`	EcoCyc:PC00004 Source assertion: The native component identifies 2 copies of PD00257. This supports reference assembly composition, not occupancy or sequence identity of every tagged assay preparation. Source location `XPath /ptools-xml/Protein/component` EcoCyc:PD00257 Source assertion: The exact native chain unification identifies UniProtKB:P0ACJ8. Source location `XPath /ptools-xml/Protein/dblink[dblink-db="UNIPROT"]`
Cra-β-D-fructofuranose 1-phosphate `EcoCyc:CPLX-127`	has_part The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference.	DNA-binding transcriptional dual regulator Cra `EcoCyc:PC00061`	EcoCyc:CPLX-127 Source assertion: The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference. Source location `XPath /ptools-xml/Protein/component`
Cra-β-D-fructofuranose 1-phosphate `EcoCyc:CPLX-127`	has_part The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference.	beta-D-fructofuranose 1-phosphate(2-) `CHEBI:138881`	EcoCyc:CPLX-127 Source assertion: The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference. Source location `XPath /ptools-xml/Protein/component` EcoCyc:FRU1P Source assertion: The native compound cross-reference grounds the exact ChEBI species used for this assembly component; a generic assay effector is not silently assigned its anomer. Source location `XPath /ptools-xml/Compound/dblink[dblink-db="CHEBI"]`
CRP-cyclic-AMP DNA-binding transcriptional dual regulator `EcoCyc:CPLX0-226`	has_part The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference.	DNA-binding transcriptional dual regulator CRP `EcoCyc:PC00004`	EcoCyc:CPLX0-226 Source assertion: The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference. Source location `XPath /ptools-xml/Protein/component`
CRP-cyclic-AMP DNA-binding transcriptional dual regulator `EcoCyc:CPLX0-226`	has_part The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference.	3',5'-cyclic AMP(1-) `CHEBI:58165`	EcoCyc:CPLX0-226 Source assertion: The native component slot links this exact ligand-bound regulator to this component. No missing ligand coefficient is supplied by inference. Source location `XPath /ptools-xml/Protein/component` EcoCyc:CAMP Source assertion: The native compound cross-reference grounds the exact ChEBI species used for this assembly component; a generic assay effector is not silently assigned its anomer. Source location `XPath /ptools-xml/Compound/dblink[dblink-db="CHEBI"]`
DNA-binding transcriptional dual regulator Cra `EcoCyc:PC00061` experimental construct: 1996 six-His FruR/Cra in binding-site selection and pfkA analysis; source-described tetramer, not a sequenced untagged MG1655 control. Exact construct details are limited to the inspected abstract; native promoter/site joins provide separate gene-specific context. Qualification evidence PMID:8858581 Source assertion: The primary abstract specifies six-His FruR, asymmetric consensus/operator binding, tetramer context and negative pfkA regulation. Source location `resultList.result[id='8858581'].abstractText`	inhibits The native mode is negative for Cra regulation of the pfkA promoter. This and REG0-4838 represent the same BS785 biological-site context rather than two independent mechanisms.	pfkA `Entrez:948412`	EcoCyc:REG0-15081 Source assertion: The native mode is negative for Cra regulation of the pfkA promoter. This and REG0-4838 represent the same BS785 biological-site context rather than two independent mechanisms. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/mode \| /ptools-xml/Regulation/regulated-entity` EcoCyc:TU0-45236 Source assertion: The exact transcription unit joins promoter PM0-46536, binding site BS785 and pfkA gene EG10699. Source location `XPath /ptools-xml/Transcription-Unit/component` PMID:8858581 Source assertion: The source specifically identifies pfkA as negatively regulated by FruR after consensus/operator binding experiments. Source location `resultList.result[id='8858581'].abstractText` Entrez:948412 Source assertion: The issuing Gene record grounds the pfkA expression endpoint, b3916 in MG1655; BW25113 or historical assay preparations remain separate. Source location `XPath /Entrezgene-Set/Entrezgene`
DNA-binding transcriptional dual regulator Cra `EcoCyc:PC00061`	inhibits Native operon-mediated fbaA repression through the epd promoter. REG0-5630 and REG0-15233 share the biological epd site context. The broader1996 FruR abstract supports the regulon, but is not used as a gene-specific quote absent from its text.	fbaA `Entrez:947415`	EcoCyc:REG0-15233 Source assertion: Native Cra regulation of the epd promoter is negative. Its effect on fbaA is carried through the epd-pgk-fbaA transcriptional unit, not a demonstrated separate fbaA operator. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/mode \| /ptools-xml/Regulation/regulated-entity` EcoCyc:TU0-45273 Source assertion: The native epd promoter transcription unit includes EG10282 (fbaA), EG10703 (pgk) and EG10368 (epd). Shared promoter entries are not distinct regulatory mechanisms. Source location `XPath /ptools-xml/Transcription-Unit/component` Entrez:947415 Source assertion: The issuing Gene record grounds fbaA/b2925 as the expression endpoint; it does not establish direct binding at an isolated fbaA promoter. Source location `XPath /Entrezgene-Set/Entrezgene`
D-fructofuranose 1-phosphate(2-) `CHEBI:58674`	inhibits Source-limited inhibition of Cra operator binding by generic F1P; assay anomer/protonation is not measured. Older FBP-effector discussions and the later negative result remain explicit. No FBP→Cra inhibition edge is inferred.	DNA-binding transcriptional dual regulator Cra `EcoCyc:PC00061` experimental construct: 2018 source-described E. coli Cra preparation in thermal-shift, microscale-thermophoresis and EMSA assays. Only the primary abstract was acquired: tag/cleavage/sequence details are unresolved. The native reference tetramer does not assert the exact assay material. Qualification evidence PMID:29923648 Source assertion: The abstract identifies thermal-shift/MST and EMSA assays on Cra, with F1P and FBP comparisons; full construct methods were not acquired. Source location `resultList.result[id='29923648'].abstractText`	PMID:29923648 Source assertion: F1P impairs Cra DNA-binding affinity, while FBP neither binds Cra nor impairs its operator binding in the reported tests. The paper also studies a distinct Bacillus CggR protein whose FBP response is not transferred to Cra. Source location `resultList.result[id='29923648'].abstractText` EcoCyc:D-fructofuranose-1-phosphate Source assertion: The independent native generic D-fructofuranose1P class links CHEBI58674. The separate FRU1P beta species belongs only to the source-defined ligand complex. Source location `XPath /ptools-xml/Compound/dblink[dblink-db="CHEBI"]`
CRP-cyclic-AMP DNA-binding transcriptional dual regulator `EcoCyc:CPLX0-226`	activates Positive native operon-associated expression effect. In the inspected1998 abstract, the glucose response is indirect; no direct fbaA-promoter activation or universal CRP sign is asserted. REG0-5629 is the same biological promoter context.	fbaA `Entrez:947415`	EcoCyc:REG0-15234 Source assertion: The native epd promoter regulation has positive mode for cAMP-CRP; the fbaA endpoint is linked by the operon, not a distinct bound fbaA promoter. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/mode \| /ptools-xml/Regulation/regulated-entity` EcoCyc:TU0-45273 Source assertion: The epd-pgk-fbaA transcription unit provides the source path to fbaA. Source location `XPath /ptools-xml/Transcription-Unit/component` PMID:9851989 Source assertion: In glucose, deleting the CRP-cAMP site had little effect, whereas crp or cya loss strongly reduced gapB/epd P0 activity. The authors infer an indirect CRP-cAMP effect under these conditions. Source location `resultList.result[id='9851989'].abstractText` Entrez:947415 Source assertion: The exact issuing fbaA record grounds the downstream operon expression endpoint. Source location `XPath /Entrezgene-Set/Entrezgene`
PTS system glucose-specific EIICB component `UniProtKB:P69786`	activates Indirect glucose/PTS-associated operon expression context via PtsG. It is not a pathway-specific S7P transporter, direct fbaA DNA interaction or a crr/EIIA assignment.	fbaA `Entrez:947415`	PMID:9851989 Source assertion: Glucose stimulation of gapB/epd P0 depends on ptsG-encoded EIIGlc. This is expression-system evidence, not a purified direct DNA-binding or enzyme-activation assay. Source location `resultList.result[id='9851989'].abstractText` EcoCyc:TU0-45273 Source assertion: The source transcription unit links the epd promoter to fbaA, preserving the indirect operon context. Source location `XPath /ptools-xml/Transcription-Unit/component` UniProtKB:P69786 Source assertion: The issuing protein entry identifies ptsG IICBGlc; the separate crr IIA chain is not substituted. Source location `entry[primaryAccession='P69786'].genes,organism,sequence` Entrez:945651 Source assertion: This is the exact ptsG subject-reference gene identity, not the fbaA object endpoint. Source location `XPath /Entrezgene-Set/Entrezgene` Entrez:947415 Source assertion: This is the fbaA expression object identity. Source location `XPath /Entrezgene-Set/Entrezgene`
RNA polymerase sigma factor RpoS `UniProtKB:P13445` experimental construct: 2009 His-tagged RpoS from pET28b+ in ER2566, combined with commercial RNAP core (core:sigma1:5) for pfkA-promoter transcription. The isolated reference sigma chain is not an autonomous polymerase; exact source construct and reconstituted system delimit this claim. Qualification evidence PMID:19838295 Source assertion: Methods distinguish purified tagged sigma-factor preparations and reconstitution with RNA polymerase core for in-vitro transcription. Source location `XPath /article/body/sec[4]/sec[9]/p[2] \| /article/body/sec[4]/sec[9]/p[3]`	activates Reconstituted RNAP with RpoS supports transcription from the tested first pfkA promoter; sigma-dependent activity belongs to the assembled assay system.	pfkA `Entrez:948412`	PMID:19838295 Source assertion: Reconstituted RNAP with RpoS supports transcription from the tested first pfkA promoter; sigma-dependent activity belongs to the assembled assay system. Source location `XPath /article/body/sec[2]/sec[6]/p[2] \| /article/body/sec[2]/sec[6]/fig[2]` Entrez:948412 Source assertion: The issuing pfkA gene is the expression endpoint; this mapping does not identify every promoter-template construct as the current reference sequence. Source location `XPath /Entrezgene-Set/Entrezgene`
RNA polymerase sigma factor RpoD `UniProtKB:P00579` experimental construct: 2009 His-tagged RpoD from pET28b+ in ER2566, combined with commercial RNAP core (core:sigma1:5) for pfkA-promoter transcription. The isolated reference sigma chain is not an autonomous polymerase; exact source construct and reconstituted system delimit this claim. Qualification evidence PMID:19838295 Source assertion: Methods distinguish purified tagged sigma-factor preparations and reconstitution with RNA polymerase core for in-vitro transcription. Source location `XPath /article/body/sec[4]/sec[9]/p[2] \| /article/body/sec[4]/sec[9]/p[3]`	activates Reconstituted RNAP with RpoD supports transcription from the tested first pfkA promoter; sigma-dependent activity belongs to the assembled assay system.	pfkA `Entrez:948412`	PMID:19838295 Source assertion: Reconstituted RNAP with RpoD supports transcription from the tested first pfkA promoter; sigma-dependent activity belongs to the assembled assay system. Source location `XPath /article/body/sec[2]/sec[6]/p[2] \| /article/body/sec[2]/sec[6]/fig[2]` Entrez:948412 Source assertion: The issuing pfkA gene is the expression endpoint; this mapping does not identify every promoter-template construct as the current reference sequence. Source location `XPath /Entrezgene-Set/Entrezgene`
RNA polymerase sigma factor RpoS `UniProtKB:P13445` experimental construct: 2009 JM101-derived PB11/PB12 ΔptsH ptsI crr backgrounds and rpoS derivatives during aerobic M9 glucose growth. The RpoS subject denotes an expression contrast, not purified binding or the BW25113 talAB bypass cohort. Qualification evidence PMID:19838295 Source assertion: The source compares JM101, PTS-deficient PB11/PB12 and their rpoS derivatives under specified glucose-growth conditions. Source location `XPath /article/body/sec[4]/sec[1]/p`	activates Condition-specific RpoS-associated fbaA expression, distinct from direct reconstituted pfkA transcription. Failure to find an immediate fbaA promoter here is not general promoter absence.	fbaA `Entrez:947415`	PMID:19838295 Source assertion: The pgk/fbaA expression and promoter analysis provides RpoS-associated context; an immediate fbaA promoter was not found under the tested conditions. Operon and indirect effects remain possible. Source location `XPath /article/body/sec[2]/sec[2]/sec[6]/p \| /article/body/sec[3]/sec[2]/p` Entrez:947415 Source assertion: The issuing fbaA gene grounds this expression endpoint, not an independently proven direct RpoS-binding site. Source location `XPath /Entrezgene-Set/Entrezgene`
Carbon storage regulator `UniProtKB:P69913` experimental construct: 2016 isogenic csrA51 hypomorph versus source wild type, M9 glucose; attenuated CsrA, not a complete deletion. Subject is a reference anchor for expression/rescue inference. The abstract/native annotation does not identify a direct pfkA RNA-binding site. Qualification evidence PMID:26833659 Source assertion: The primary abstract compares a CsrA-attenuated strain to its wild type, with PfkA restoration/rescue; it does not specify a direct pfkA RNA-binding site. Source location `resultList.result[id='26833659'].abstractText` EcoCyc:6PFK-1-CPX Source assertion: The native comment explicitly identifies the csrA51 hypomorphic allele and M9 glucose context. Source location `XPath /ptools-xml/Protein/comment`	activates CsrA attenuation disrupts upper glycolysis; restoring PfkA activity suppresses glucose-phosphate stress and increases growth. This supports a positive expression contribution, not a new physical RNA-binding claim.	pfkA `Entrez:948412`	PMID:26833659 Source assertion: CsrA attenuation disrupts upper glycolysis; restoring PfkA activity suppresses glucose-phosphate stress and increases growth. This supports a positive expression contribution, not a new physical RNA-binding claim. Source location `resultList.result[id='26833659'].abstractText` EcoCyc:6PFK-1-CPX Source assertion: The source states that pfkA expression is reduced in csrA51 and that PfkA overexpression partially rescues its growth defect. Source location `XPath /ptools-xml/Protein/comment` Entrez:947176 Source assertion: The exact issuing csrA gene grounds the subject-reference mapping, not the pfkA object. Source location `XPath /Entrezgene-Set/Entrezgene` Entrez:948412 Source assertion: The exact issuing pfkA gene grounds the expression object. Source location `XPath /Entrezgene-Set/Entrezgene`
Cytochrome bo(3) ubiquinol oxidase subunit 2 `UniProtKB:P0ABJ1` experimental construct: 2011 BW25113 Keio cyoA deletion versus source wild type in aerobic continuous glucose culture: D0.2 h−1,37 °C,pH7,DO35–40%, C/N1.68 or8.42. Reference protein is an anchor for indirect knockout inference, not a tested purified active-state species. Qualification evidence PMID:21272324 Source assertion: Methods identify BW25113 Keio single deletions and the aerobic continuous-culture conditions; multiple network effects can mediate expression changes. Source location `XPath /collection/document/passage[51]`	inhibits Conditional transcript effect from a single-deletion comparison, not direct DNA binding or evidence of a universal regulatory sign. The Fnr contrast under oxygen does not imply the canonical anaerobic [4Fe-4S] active state. C/N-specific comparisons and network interpretations remain in source context.	pfkA `Entrez:948412`	PMID:21272324 Source assertion: The cyoA deletion comparison reports increased pfkA transcript. The negative reference-associated expression sign is inferred from the loss-of-function contrast and may be indirect; no pfkA binding experiment is supplied. Source location `XPath /collection/document/passage[19] \| /collection/document/passage[35]` Entrez:945080 Source assertion: The issuing cyoA gene grounds this subject-reference mapping. It is not the pfkA expression endpoint. Source location `XPath /Entrezgene-Set/Entrezgene` UniProtKB:P0ABJ1 Source assertion: The issuing entry links cyoA to this exact reference protein; it does not establish that the deletion assay contained an isolated active assembly. Source location `entry[primaryAccession='P0ABJ1'].genes,organism,sequence` Entrez:948412 Source assertion: The issuing pfkA gene is the expression object. Source location `XPath /Entrezgene-Set/Entrezgene`
Cytochrome bd-I ubiquinol oxidase subunit 2 `UniProtKB:P0ABK2` experimental construct: 2011 BW25113 Keio cydB deletion versus source wild type in aerobic continuous glucose culture: D0.2 h−1,37 °C,pH7,DO35–40%, C/N1.68 or8.42. Reference protein is an anchor for indirect knockout inference, not a tested purified active-state species. Qualification evidence PMID:21272324 Source assertion: Methods identify BW25113 Keio single deletions and the aerobic continuous-culture conditions; multiple network effects can mediate expression changes. Source location `XPath /collection/document/passage[51]`	inhibits Conditional transcript effect from a single-deletion comparison, not direct DNA binding or evidence of a universal regulatory sign. The Fnr contrast under oxygen does not imply the canonical anaerobic [4Fe-4S] active state. C/N-specific comparisons and network interpretations remain in source context.	pfkA `Entrez:948412`	PMID:21272324 Source assertion: The cydB deletion comparison reports increased pfkA transcript. The negative reference-associated expression sign is inferred from the loss-of-function contrast and may be indirect; no pfkA binding experiment is supplied. Source location `XPath /collection/document/passage[19] \| /collection/document/passage[35]` Entrez:945347 Source assertion: The issuing cydB gene grounds this subject-reference mapping. It is not the pfkA expression endpoint. Source location `XPath /Entrezgene-Set/Entrezgene` UniProtKB:P0ABK2 Source assertion: The issuing entry links cydB to this exact reference protein; it does not establish that the deletion assay contained an isolated active assembly. Source location `entry[primaryAccession='P0ABK2'].genes,organism,sequence` Entrez:948412 Source assertion: The issuing pfkA gene is the expression object. Source location `XPath /Entrezgene-Set/Entrezgene`
Fumarate and nitrate reduction regulatory protein `UniProtKB:P0A9E5` experimental construct: 2011 BW25113 Keio fnr deletion versus source wild type in aerobic continuous glucose culture: D0.2 h−1,37 °C,pH7,DO35–40%, C/N1.68 or8.42. Reference protein is an anchor for indirect knockout inference, not a tested purified active-state species. Qualification evidence PMID:21272324 Source assertion: Methods identify BW25113 Keio single deletions and the aerobic continuous-culture conditions; multiple network effects can mediate expression changes. Source location `XPath /collection/document/passage[51]`	inhibits Conditional transcript effect from a single-deletion comparison, not direct DNA binding or evidence of a universal regulatory sign. The Fnr contrast under oxygen does not imply the canonical anaerobic [4Fe-4S] active state. C/N-specific comparisons and network interpretations remain in source context.	pfkA `Entrez:948412`	PMID:21272324 Source assertion: The fnr deletion comparison reports increased pfkA transcript. The negative reference-associated expression sign is inferred from the loss-of-function contrast and may be indirect; no pfkA binding experiment is supplied. Source location `XPath /collection/document/passage[25] \| /collection/document/passage[37]` Entrez:945908 Source assertion: The issuing fnr gene grounds this subject-reference mapping. It is not the pfkA expression endpoint. Source location `XPath /Entrezgene-Set/Entrezgene` UniProtKB:P0A9E5 Source assertion: The issuing entry links fnr to this exact reference protein; it does not establish that the deletion assay contained an isolated active assembly. Source location `entry[primaryAccession='P0A9E5'].genes,organism,sequence` Entrez:948412 Source assertion: The issuing pfkA gene is the expression object. Source location `XPath /Entrezgene-Set/Entrezgene`
Ferric uptake regulation protein `UniProtKB:P0A9A9` experimental construct: 2011 BW25113 Keio fur deletion versus source wild type in aerobic continuous glucose culture: D0.2 h−1,37 °C,pH7,DO35–40%, C/N1.68 or8.42. Reference protein is an anchor for indirect knockout inference, not a tested purified active-state species. Qualification evidence PMID:21272324 Source assertion: Methods identify BW25113 Keio single deletions and the aerobic continuous-culture conditions; multiple network effects can mediate expression changes. Source location `XPath /collection/document/passage[51]`	inhibits Conditional transcript effect from a single-deletion comparison, not direct DNA binding or evidence of a universal regulatory sign. The Fnr contrast under oxygen does not imply the canonical anaerobic [4Fe-4S] active state. C/N-specific comparisons and network interpretations remain in source context.	pfkA `Entrez:948412`	PMID:21272324 Source assertion: The fur deletion comparison reports increased pfkA transcript. The negative reference-associated expression sign is inferred from the loss-of-function contrast and may be indirect; no pfkA binding experiment is supplied. Source location `XPath /collection/document/passage[29]` Entrez:945295 Source assertion: The issuing fur gene grounds this subject-reference mapping. It is not the pfkA expression endpoint. Source location `XPath /Entrezgene-Set/Entrezgene` UniProtKB:P0A9A9 Source assertion: The issuing entry links fur to this exact reference protein; it does not establish that the deletion assay contained an isolated active assembly. Source location `entry[primaryAccession='P0A9A9'].genes,organism,sequence` Entrez:948412 Source assertion: The issuing pfkA gene is the expression object. Source location `XPath /Entrezgene-Set/Entrezgene`
beta-D-fructofuranose 6-phosphate(2-) `CHEBI:57634`	activates Positive cooperative response to canonical F6P substrate; this does not establish that F6P activates S7P phosphorylation or imply a separate allosteric ligand mechanism.	6-phosphofructokinase 1 `EcoCyc:6PFK-1-CPX`	EcoCyc:REG0-7476 Source assertion: The native positive regulation names FRUCTOSE-6P for canonical phosphofructokinase activity. This preserves cooperative substrate response, not an independent S7P-effector experiment. Source location `XPath /ptools-xml/Regulation/regulator \| /ptools-xml/Regulation/mode \| /ptools-xml/Regulation/regulated-entity` EcoCyc:FRUCTOSE-6P Source assertion: The exact native compound identifies beta-D-fructofuranose6-phosphate with CHEBI57634, charge−2 and matching formula/InChI. Its inconsistent CML SMILES is not used to override the native identity. Source location `XPath /ptools-xml/Compound/common-name \| /ptools-xml/Compound/dblink[dblink-db="CHEBI"] \| /ptools-xml/Compound/cml \| /ptools-xml/Compound/inchi`
`MetaCyc:PWY0-1517`	has_part The exact frozen native bypass root attaches this named child. This is source structural membership, not an extra core reaction, transport or independently inferred causal direction.	Pentose Phosphate `PathBank:SMP0121065`	PathBank:SMP0002110 Source assertion: The exact frozen native bypass root attaches this named child. This is source structural membership, not an extra core reaction, transport or independently inferred causal direction. Source location `XPath //[local-name()="Pathway"][@[local-name()="about"]="http://identifiers.org/smpdb/SMP0002110"]/[local-name()="pathwayComponent"][@[local-name()="resource"]="http://identifiers.org/smpdb/SMP0121065"]`
`MetaCyc:PWY0-1517`	has_part The exact frozen native bypass root attaches this named child. This is source structural membership, not an extra core reaction, transport or independently inferred causal direction.	Glycolysis and Pyruvate Dehydrogenase `PathBank:SMP0000807`	PathBank:SMP0002110 Source assertion: The exact frozen native bypass root attaches this named child. This is source structural membership, not an extra core reaction, transport or independently inferred causal direction. Source location `XPath //[local-name()="Pathway"][@[local-name()="about"]="http://identifiers.org/smpdb/SMP0002110"]/[local-name()="pathwayComponent"][@[local-name()="resource"]="http://identifiers.org/smpdb/SMP0000807"]`
Pentose Phosphate `PathBank:SMP0121065`	has_part Unsigned structural participant context, using the exact native local compound. Native neutral S7P/E4P and dilithium DHAP remain distinct from the Rhea anions. The generic Interaction supplies no transport mechanism, regulatory sign or extra stoichiometric conversion.	D-Sedoheptulose 7-phosphate `PathBank:SMP0002110/Compound/PW_C000843`	PathBank:SMP0002110 Source assertion: This child has a generic Interaction whose sole participant is exact local compound PW_C000843, associated with S7P input to the bypass. A source SubPathwayInput/Output marker is not inhibition or a biochemical side. Source location `XPath //[local-name()="Pathway"][@[local-name()="about"]="http://identifiers.org/smpdb/SMP0121065"] \| //[local-name()="Interaction"][@[local-name()="ID"]="SubPathwayInteractions/109963"] \| //[local-name()="SmallMolecule"][@[local-name()="ID"]="Compound/PW_C000843"] \| //[local-name()="SmallMoleculeReference"][@[local-name()="ID"]="CompoundReference/PW_C000843"]`
Pentose Phosphate `PathBank:SMP0121065`	has_part Unsigned structural participant context, using the exact native local compound. Native neutral S7P/E4P and dilithium DHAP remain distinct from the Rhea anions. The generic Interaction supplies no transport mechanism, regulatory sign or extra stoichiometric conversion.	D-Erythrose 4-phosphate `PathBank:SMP0002110/Compound/PW_C001019`	PathBank:SMP0002110 Source assertion: This child has a generic Interaction whose sole participant is exact local compound PW_C001019, associated with E4P output from the bypass. A source SubPathwayInput/Output marker is not inhibition or a biochemical side. Source location `XPath //[local-name()="Pathway"][@[local-name()="about"]="http://identifiers.org/smpdb/SMP0121065"] \| //[local-name()="Interaction"][@[local-name()="ID"]="SubPathwayInteractions/109888"] \| //[local-name()="SmallMolecule"][@[local-name()="ID"]="Compound/PW_C001019"] \| //[local-name()="SmallMoleculeReference"][@[local-name()="ID"]="CompoundReference/PW_C001019"]`
Glycolysis and Pyruvate Dehydrogenase `PathBank:SMP0000807`	has_part Unsigned structural participant context, using the exact native local compound. Native neutral S7P/E4P and dilithium DHAP remain distinct from the Rhea anions. The generic Interaction supplies no transport mechanism, regulatory sign or extra stoichiometric conversion.	Glycerone phosphate `PathBank:SMP0002110/Compound/PW_C042631`	PathBank:SMP0002110 Source assertion: This child has a generic Interaction whose sole participant is exact local compound PW_C042631, associated with DHAP output from the bypass. A source SubPathwayInput/Output marker is not inhibition or a biochemical side. Source location `XPath //[local-name()="Pathway"][@[local-name()="about"]="http://identifiers.org/smpdb/SMP0000807"] \| //[local-name()="Interaction"][@[local-name()="ID"]="SubPathwayInteractions/109887"] \| //[local-name()="SmallMolecule"][@[local-name()="ID"]="Compound/PW_C042631"] \| //[local-name()="SmallMoleculeReference"][@[local-name()="ID"]="CompoundReference/PW_C042631"]`

References

MetaCyc:PWY0-1517 MetaCyc PWY0-1517: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
RHEA:31444 Rhea RHEA:31444 exact directional reaction (source version: Rhea142 full original RDF; native directional side and containsN projection; SQL label authority separately Rhea139)
RHEA:30169 Rhea RHEA:30169 exact directional reaction (source version: Rhea142 full original RDF; native directional side and containsN projection; SQL label authority separately Rhea139)
EcoCyc:ENZRXN0-7407 EcoCyc ENZRXN0-7407: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:ENZRXN0-7406 EcoCyc ENZRXN0-7406: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:6PFK-1-CPX EcoCyc 6PFK-1-CPX: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:6PFK-1-MONOMER EcoCyc 6PFK-1-MONOMER: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
UniProtKB:P0A796 ATP-dependent 6-phosphofructokinase isozyme 1 (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
EcoCyc:FRUCBISALD-CLASSII EcoCyc FRUCBISALD-CLASSII: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:FRUCTBISALD-CLASSII-MONOMER EcoCyc FRUCTBISALD-CLASSII-MONOMER: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
UniProtKB:P0AB71 Fructose-bisphosphate aldolase class 2 (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
PMID:19756045 Systematic phenome analysis of Escherichia coli multiple-knockout mutants reveals hidden reactions in central carbon metabolism (source version: Full retained primary JATS/BioC XML; original paragraph selectors. Supplementary originals are separately bound when expressly cited.)
PMID:31871051 The pentose phosphate pathway of cellulolytic clostridia relies on 6-phosphofructokinase instead of transaldolase (source version: Full retained primary JATS/BioC XML; original paragraph selectors. Supplementary originals are separately bound when expressly cited.)
PMID:8436219 Identification of zinc-binding ligands in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
EcoCyc:REG0-7473 EcoCyc REG0-7473: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:REG0-7474 EcoCyc REG0-7474: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:REG0-7475 EcoCyc REG0-7475: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:REG0-12168 EcoCyc REG0-12168: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:F16ALDOLASE-ENZRXN-CLASSII EcoCyc F16ALDOLASE-ENZRXN-CLASSII: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:REG0-12169 EcoCyc REG0-12169: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:REG0-8470 EcoCyc REG0-8470: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
PMID:22014167 Fructose- 1,6-bisphosphate aldolase (class II) is the primary site of nickel toxicity in Escherichia coli (source version: Full retained primary JATS/BioC XML; original paragraph selectors. Supplementary originals are separately bound when expressly cited.)
PMID:31464375 Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli (source version: Full retained primary JATS/BioC XML; original paragraph selectors. Supplementary originals are separately bound when expressly cited.)
EcoCyc:PC00061 EcoCyc PC00061: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:PD00521 EcoCyc PD00521: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:PC00004 EcoCyc PC00004: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:PD00257 EcoCyc PD00257: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:CPLX-127 EcoCyc CPLX-127: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:FRU1P EcoCyc FRU1P: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:CPLX0-226 EcoCyc CPLX0-226: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:CAMP EcoCyc CAMP: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
PMID:8858581 Definition of a consensus DNA-binding site for the Escherichia coli pleiotropic regulatory protein, FruR. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
EcoCyc:REG0-15081 EcoCyc REG0-15081: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:TU0-45236 EcoCyc TU0-45236: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
Entrez:948412 pfkA: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
EcoCyc:REG0-15233 EcoCyc REG0-15233: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:TU0-45273 EcoCyc TU0-45273: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
Entrez:947415 fbaA: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
PMID:29923648 Assessment of the interaction between the flux-signaling metabolite fructose-1,6-bisphosphate and the bacterial transcription factors CggR and Cra. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
EcoCyc:D-fructofuranose-1-phosphate EcoCyc D-fructofuranose-1-phosphate: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:REG0-15234 EcoCyc REG0-15234: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
PMID:9851989 The EIIGlc protein is involved in glucose-mediated activation of Escherichia coli gapA and gapB-pgk transcription. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
UniProtKB:P69786 PTS system glucose-specific EIICB component (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
Entrez:945651 ptsG: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
PMID:19838295 Transcription Analysis of Central Metabolism Genes in Escherichia coli . Possible Roles of σ 38 in Their Expression, as a Response to Carbon Limitation (source version: Full retained primary JATS/BioC XML; original paragraph selectors. Supplementary originals are separately bound when expressly cited.)
PMID:26833659 The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
Entrez:947176 csrA: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
PMID:21272324 Transcriptional regulation of main metabolic pathways of cyoA, cydB, fnr, and fur gene knockout Escherichia coli in C-limited and N-limited aerobic continuous cultures (source version: Full retained primary JATS/BioC XML; original paragraph selectors. Supplementary originals are separately bound when expressly cited.)
Entrez:945080 cyoA: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
UniProtKB:P0ABJ1 Cytochrome bo(3) ubiquinol oxidase subunit 2 (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
Entrez:945347 cydB: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
UniProtKB:P0ABK2 Cytochrome bd-I ubiquinol oxidase subunit 2 (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
Entrez:945908 fnr: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
UniProtKB:P0A9E5 Fumarate and nitrate reduction regulatory protein (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
Entrez:945295 fur: exact issuing Gene record (source version: Native Entrezgene XML; exact issuing GeneID, organism and locus; retrieved2026-10-12)
UniProtKB:P0A9A9 Ferric uptake regulation protein (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
EcoCyc:REG0-7476 EcoCyc REG0-7476: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:FRUCTOSE-6P EcoCyc FRUCTOSE-6P: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:HIS EcoCyc HIS: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
EcoCyc:GLUTATHIONE EcoCyc GLUTATHIONE: native original (source version: PGDB27.0; exact unmodified native XML; retrieved2026-10-12; source evidence and scope retained)
PathBank:SMP0002110 Sedoheptulose Bisphosphate Bypass: frozen native root and child interfaces (source version: Frozen whole PathBank primary BioPAX ZIP, memberPW002098.owl/rootSMP0002110; archive/member hashes separately bound; not a live per-pathway download)
EcoCyc:PWY0-1517 EcoCyc:PWY0-1517: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
MetaCyc:RXN0-6541 MetaCyc:RXN0-6541: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
MetaCyc:SEDOBISALDOL-RXN MetaCyc:SEDOBISALDOL-RXN: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
MetaCyc:D-SEDOHEPTULOSE-7-P MetaCyc:D-SEDOHEPTULOSE-7-P: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
MetaCyc:CPD-19339 MetaCyc:CPD-19339: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
MetaCyc:D-SEDOHEPTULOSE-1-7-P2 MetaCyc:D-SEDOHEPTULOSE-1-7-P2: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
DOI:10.18174/510683 The Thermophilic Route to Succinic Acid: author thesis, chapter6 supporting information (source version: 2020 doctoral thesis; complete original PDF; chapter6 supporting FiguresS1–S5 distinct from inaccessible journal-supplement bytes)
MetaCyc:PWY-8178 MetaCyc:PWY-8178: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
MetaCyc:RXN-21730 MetaCyc:RXN-21730: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
EcoCyc:6PFRUCTPHOS-ENZRXN EcoCyc:6PFRUCTPHOS-ENZRXN: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
PMID:6996735 Comparison of the mechanisms of two distinct aldolases from Escherichia coli grown on gluconeogenic substrates. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
EcoCyc:REG0-12167 EcoCyc:REG0-12167: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
PMID:7872790 Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:12595741 The organization of divalent cations in the active site of cadmium Escherichia coli fructose-1,6-bisphosphate aldolase. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:3281666 Phosphate modification of fructose-1,6-bisphosphate aldolase in Escherichia coli. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:7851430 A reactive, surface cysteine residue of the class-II fructose-1,6-bisphosphate aldolase of Escherichia coli revealed by electrospray ionisation mass spectrometry. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:35636362 Selective enrichment tandem β-elimination assisted strategy for N-phosphorylation analysis. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:16236509 N-Sulfonyl hydroxamate derivatives as inhibitors of class II fructose-1,6-diphosphate aldolase. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:27065204 Systematic Identification of Protein-Metabolite Interactions in Complex Metabolite Mixtures by Ligand-Detected Nuclear Magnetic Resonance Spectroscopy. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
EcoCyc:REG0-4838 EcoCyc:REG0-4838: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
EcoCyc:REG0-5630 EcoCyc:REG0-5630: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
PMID:8577250 The global regulatory protein FruR modulates the direction of carbon flow in Escherichia coli. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:8195118 In vitro asymmetric binding of the pleiotropic regulatory protein, FruR, to the ace operator controlling glyoxylate shunt enzyme synthesis. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:30019355 The imbroglio of the physiological Cra effector clarified at last. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:34666048 Deciphering the enigma of missing DNA binding domain of LacI family transcription factors. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
EcoCyc:REG0-5629 EcoCyc:REG0-5629: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
UniProtKB:P69783 PTS system glucose-specific EIIA component (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
UniProtKB:P13445 RNA polymerase sigma factor RpoS (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
UniProtKB:P69913 Carbon storage regulator (source version: Complete issuing UniProt original; exact accession selector for batch query; retrieved2026-10-12; entryAudit retained)
PMID:16102000 Characterization of the molecular mechanisms involved in the differential production of erythrose-4-phosphate dehydrogenase, 3-phosphoglycerate kinase and class II fructose-1,6-bisphosphate aldolase in Escherichia coli. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
PMID:23274360 Effect of acidic condition on the metabolic regulation of Escherichia coli and its phoB mutant. (source version: EuropePMC original primary metadata/abstract response; exact PMID selector; full paper not acquired for this claim)
EcoCyc:TU0-45239 EcoCyc:TU0-45239: native original (source version: PGDB27.0; exact original XML; retrieved2026-10-12; source annotation scope retained)
PMID:36286488 Increasing the Thermodynamic Driving Force of the Phosphofructokinase Reaction in Clostridium thermocellum (source version: 2022 publisher-rendered tool receipt; bounded Results/Discussion read for donor-route comparison; not local raw HTML or complete author-review body access)

Curation history

2026-10-12T06:41:39Z codex
- CREATE — Curate the ATP-dependent sedoheptulose-bisphosphate bypass with source-scoped mechanism evidence.
  Prepared and independently assessed the exact MetaCyc:PWY0-1517 scientific successor (SHA256 cd59859d1dbcbc6c36961822b02daebc519a80a224ba8fa63d3235933b328101): two reaction events, eight chemical-side occurrences, 67 mechanistic edges, 94 references and 24 endpoint qualifiers. E. coli PfkA and FbaA identities, mutant and wild-type flux contexts, assay substrates, protein preparations, metal conditions and indirect regulatory evidence remain distinguished. Four findings tracked as issues 450-453 were corrected and independently reassessed: the HisTrap and strain/growth Methods locators, native InChI selectors, and the 2009 Table III distinction between a blank not-determined E4P cell and an explicit not-detected result. The final record has the same biological graph identities as the original draft. Actual full native source and ontology builds used these exact final target bytes and passed independent output review, producing 2474 source terms, 595 source metadata objects, 1963 ontology terms and five ontology metadata objects while preserving prior authority objects and native source ordering. The accepted actual native serialization is adopted, with the original findings, exact six-field correction, primary-original bindings, full build execution and independent reviews retained in the research dossier. Computational expression-module evidence and primary-source uncertainty remain bounded. This event records completed scientific and authority preparation and adoption; maintained gates, saved review, page QA, issue closure and merge remain subsequent lifecycle actions.
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2026-10-12T07:07:33Z codex
- EDIT — Trim trailing whitespace from the ATP bypass bibliography title.
  Issue460: the actual rendered page exposed trailing whitespace from the source-derived PMID:31464375 title. Applied only rstrip to references[22].title, retaining substantive wording, all identifiers, source hashes, edge and qualifier evidence, and scientific scope. Independent native consumers confirm unchanged 62 source and 36 ontology selectors, exact KGX nodes and only three ATP bibliography metadata cells on sbp-040, sbp-041 and sbp-042 changing. The full native build and original maintained gates remain historical observations of cd59859d target bytes. This real corrective curation event precedes rerendering; current corrective checks, saved review, commit, issue closure and merge remain subsequent work.
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