dTDP-rhamnose biosynthetic process

GO:0019305

The complete four-step dTDP-L-rhamnose pathway converts alpha-D-glucose 1-phosphate and dTTP to dTDP-beta-L-rhamnose through thymidylyl transfer, dehydration, C3/C5 epimerization and NADPH-dependent reduction. It follows MetaCyc DTDPRHAMSYN-PWY, with the final reductase selected in the biosynthetic reverse direction of its written Rhea master equation. The protein scope is E. coli K-12. RmlA has direct biochemical and tetramer evidence; RmlB catalysis, dimerization and bound NAD are annotated by similarity to the RffG paralog. K-12 mutant extracts support RmlC function and a free 4-keto-rhamnose intermediate, while purified-enzyme stereochemical work in that study used M. tuberculosis. RmlD remains a probable K-12 pathway assignment with catalytic, magnesium and homodimer annotations by similarity to Salmonella RmlD. Functional RmlC/RmlD edges do not establish isolated-monomer sufficiency or an obligatory joint complex. RmlD NADH use is also annotated by similarity; the native NADPH route is represented here. Many K-12 lines are O-antigen deficient because of rfb-region mutations, so this pathway assignment does not imply O-antigen production in every K-12 derivative. The boundary ends at the nucleotide sugar; RffG/RffH compensation, enterobacterial common-antigen synthesis and downstream rhamnosyl transfer are separate.

Pathway type

dtdp l rhamnose biosynthesis

Organism scope

Escherichia coli K-12 NCBITaxon:83333

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Pathway network

24 nodes · 31 asserted directed edges

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Reaction / activity
Chemical / cofactor
Protein / complex
Pathway
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Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli K-12 `NCBITaxon:83333`	taxon
dTTP(4-) `CHEBI:37568`	small molecule
alpha-D-glucose 1-phosphate(2-) `CHEBI:58601`	small molecule
hydron `CHEBI:15378`	small molecule
dTDP-alpha-D-glucose(2-) `CHEBI:57477`	small molecule
diphosphate(3-) `CHEBI:33019`	small molecule
dTDP-4-dehydro-6-deoxy-alpha-D-glucose(2-) `CHEBI:57649`	small molecule
water `CHEBI:15377`	small molecule
dTDP-4-dehydro-beta-L-rhamnose(2-) `CHEBI:62830`	small molecule
NADPH(4-) `CHEBI:57783`	small molecule
dTDP-6-deoxy-beta-L-mannose(2-) `CHEBI:57510`	small molecule
NADP(3-) `CHEBI:58349`	small molecule
magnesium(2+) `CHEBI:18420`	cofactor
NAD(1-) `CHEBI:57540`	cofactor
Glucose-1-phosphate thymidylyltransferase 1 `UniProtKB:P37744`	protein
dTDP-glucose 4,6-dehydratase 1 `UniProtKB:P37759`	protein
dTDP-4-dehydrorhamnose 3,5-epimerase `UniProtKB:P37745`	protein
dTDP-4-dehydrorhamnose reductase `UniProtKB:P37760`	protein
dTDP-glucose pyrophosphorylase `MetaCyc:CPLX0-8034`	complex
dTDP-glucose 4,6-dehydratase 1 `MetaCyc:DTDPGLUCDEHYDRAT-CPLX`	complex
dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	molecular activity	left to right
dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	molecular activity	left to right
dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose `RHEA:16970`	molecular activity	left to right
dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	molecular activity	right to left

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
dTTP(4-) `CHEBI:37568`	consumes	dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	RHEA:15226 Source assertion: RHEA:15226 assigns CHEBI:37568 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/15226 rh:substrates; http://rdf.rhea-db.org/15225_L rh:contains1 http://rdf.rhea-db.org/Participant_15225_compound_6436; http://rdf.rhea-db.org/Participant_15225_compound_6436 rh:compound http://rdf.rhea-db.org/Compound_6436; rh:chebi`
alpha-D-glucose 1-phosphate(2-) `CHEBI:58601`	consumes	dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	RHEA:15226 Source assertion: RHEA:15226 assigns CHEBI:58601 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/15226 rh:substrates; http://rdf.rhea-db.org/15225_L rh:contains1 http://rdf.rhea-db.org/Participant_15225_compound_3943; http://rdf.rhea-db.org/Participant_15225_compound_3943 rh:compound http://rdf.rhea-db.org/Compound_3943; rh:chebi`
hydron `CHEBI:15378`	consumes	dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	RHEA:15226 Source assertion: RHEA:15226 assigns CHEBI:15378 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/15226 rh:substrates; http://rdf.rhea-db.org/15225_L rh:contains1 http://rdf.rhea-db.org/Participant_15225_compound_3249; http://rdf.rhea-db.org/Participant_15225_compound_3249 rh:compound http://rdf.rhea-db.org/Compound_3249; rh:chebi`
dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	produces	dTDP-alpha-D-glucose(2-) `CHEBI:57477`	RHEA:15226 Source assertion: RHEA:15226 assigns CHEBI:57477 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/15226 rh:products; http://rdf.rhea-db.org/15225_R rh:contains1 http://rdf.rhea-db.org/Participant_15225_compound_3802; http://rdf.rhea-db.org/Participant_15225_compound_3802 rh:compound http://rdf.rhea-db.org/Compound_3802; rh:chebi`
dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	produces	diphosphate(3-) `CHEBI:33019`	RHEA:15226 Source assertion: RHEA:15226 assigns CHEBI:33019 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/15226 rh:products; http://rdf.rhea-db.org/15225_R rh:contains1 http://rdf.rhea-db.org/Participant_15225_compound_2106; http://rdf.rhea-db.org/Participant_15225_compound_2106 rh:compound http://rdf.rhea-db.org/Compound_2106; rh:chebi`
dTDP-alpha-D-glucose(2-) `CHEBI:57477`	consumes	dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	RHEA:17222 Source assertion: RHEA:17222 assigns CHEBI:57477 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/17222 rh:substrates; http://rdf.rhea-db.org/17221_L rh:contains1 http://rdf.rhea-db.org/Participant_17221_compound_3802; http://rdf.rhea-db.org/Participant_17221_compound_3802 rh:compound http://rdf.rhea-db.org/Compound_3802; rh:chebi`
dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	produces	dTDP-4-dehydro-6-deoxy-alpha-D-glucose(2-) `CHEBI:57649`	RHEA:17222 Source assertion: RHEA:17222 assigns CHEBI:57649 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/17222 rh:products; http://rdf.rhea-db.org/17221_R rh:contains1 http://rdf.rhea-db.org/Participant_17221_compound_4008; http://rdf.rhea-db.org/Participant_17221_compound_4008 rh:compound http://rdf.rhea-db.org/Compound_4008; rh:chebi`
dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	produces	water `CHEBI:15377`	RHEA:17222 Source assertion: RHEA:17222 assigns CHEBI:15377 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/17222 rh:products; http://rdf.rhea-db.org/17221_R rh:contains1 http://rdf.rhea-db.org/Participant_17221_compound_1283; http://rdf.rhea-db.org/Participant_17221_compound_1283 rh:compound http://rdf.rhea-db.org/Compound_1283; rh:chebi`
dTDP-4-dehydro-6-deoxy-alpha-D-glucose(2-) `CHEBI:57649`	consumes	dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose `RHEA:16970`	RHEA:16970 Source assertion: RHEA:16970 assigns CHEBI:57649 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/16970 rh:substrates; http://rdf.rhea-db.org/16969_L rh:contains1 http://rdf.rhea-db.org/Participant_16969_compound_4008; http://rdf.rhea-db.org/Participant_16969_compound_4008 rh:compound http://rdf.rhea-db.org/Compound_4008; rh:chebi`
dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose `RHEA:16970`	produces	dTDP-4-dehydro-beta-L-rhamnose(2-) `CHEBI:62830`	RHEA:16970 Source assertion: RHEA:16970 assigns CHEBI:62830 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/16970 rh:products; http://rdf.rhea-db.org/16969_R rh:contains1 http://rdf.rhea-db.org/Participant_16969_compound_7498; http://rdf.rhea-db.org/Participant_16969_compound_7498 rh:compound http://rdf.rhea-db.org/Compound_7498; rh:chebi`
dTDP-4-dehydro-beta-L-rhamnose(2-) `CHEBI:62830`	consumes	dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	RHEA:21798 Source assertion: RHEA:21798 assigns CHEBI:62830 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/21798 rh:substrates; http://rdf.rhea-db.org/21796_R rh:contains1 http://rdf.rhea-db.org/Participant_21796_compound_7498; http://rdf.rhea-db.org/Participant_21796_compound_7498 rh:compound http://rdf.rhea-db.org/Compound_7498; rh:chebi`
NADPH(4-) `CHEBI:57783`	consumes	dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	RHEA:21798 Source assertion: RHEA:21798 assigns CHEBI:57783 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/21798 rh:substrates; http://rdf.rhea-db.org/21796_R rh:contains1 http://rdf.rhea-db.org/Participant_21796_compound_3438; http://rdf.rhea-db.org/Participant_21796_compound_3438 rh:compound http://rdf.rhea-db.org/Compound_3438; rh:chebi`
hydron `CHEBI:15378`	consumes	dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	RHEA:21798 Source assertion: RHEA:21798 assigns CHEBI:15378 to its substrates, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/21798 rh:substrates; http://rdf.rhea-db.org/21796_R rh:contains1 http://rdf.rhea-db.org/Participant_21796_compound_3249; http://rdf.rhea-db.org/Participant_21796_compound_3249 rh:compound http://rdf.rhea-db.org/Compound_3249; rh:chebi`
dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	produces	dTDP-6-deoxy-beta-L-mannose(2-) `CHEBI:57510`	RHEA:21798 Source assertion: RHEA:21798 assigns CHEBI:57510 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/21798 rh:products; http://rdf.rhea-db.org/21796_L rh:contains1 http://rdf.rhea-db.org/Participant_21796_compound_1098; http://rdf.rhea-db.org/Participant_21796_compound_1098 rh:compound http://rdf.rhea-db.org/Compound_1098; rh:chebi`
dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	produces	NADP(3-) `CHEBI:58349`	RHEA:21798 Source assertion: RHEA:21798 assigns CHEBI:58349 to its products, coefficient 1 via rh:contains1. Source location `http://rdf.rhea-db.org/21798 rh:products; http://rdf.rhea-db.org/21796_L rh:contains1 http://rdf.rhea-db.org/Participant_21796_compound_5188; http://rdf.rhea-db.org/Participant_21796_compound_5188 rh:compound http://rdf.rhea-db.org/Compound_5188; rh:chebi`
dTDP-glucose pyrophosphorylase `MetaCyc:CPLX0-8034`	catalyzes The native tetramer is the catalytic entity; the biosynthetic direction is selected without denying experimentally measured reverse pyrophosphorolysis.	dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	UniProtKB:P37744 Source assertion: P37744 explicitly links catalytic RHEA:15225 and formation of dTDP-glucose from dTTP and glucose 1-phosphate, with ECO:0000269 PMID:11697907. Source location `/comments/0; /comments/1/reaction` RHEA:15226 Source assertion: RHEA:15225 explicitly links directionalReaction RHEA:15226; this is the selected biosynthetic member. Source location `http://rdf.rhea-db.org/15225 rh:directionalReaction http://rdf.rhea-db.org/15226` MetaCyc:CPLX0-8034 Source assertion: CPLX0-8034 catalyzes DTDPGLUCOSEPP-RXN through DTDPGLUCOSEPP-ENZRXN. Source location `Protein[@frameid="CPLX0-8034"]/catalyzes/Enzymatic-Reaction/reaction` PMID:11697907 Source assertion: The indexed primary abstract reports kinetic analysis of E. coli glucose-1-phosphate thymidylyltransferase in both biosynthesis and pyrophosphorolysis directions. Source location `/resultList/result[id="11697907"]/abstractText`
dTDP-glucose 4,6-dehydratase 1 `MetaCyc:DTDPGLUCDEHYDRAT-CPLX`	catalyzes Reviewed functional inference is retained at its stated tier. Direct RffG experiments and the older E. coli B mass measurement are not relabeled as K-12 RmlB measurements.	dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	UniProtKB:P37759 Source assertion: P37759 links RHEA:17221 and oxidation/dehydration/rereduction of dTDP-glucose with ECO:0000250 UniProtKB:P27830; this is an inference from RffG, not a purified K-12 RmlB assay. Source location `/comments/0; /comments/1/reaction` RHEA:17222 Source assertion: RHEA:17221 explicitly links directionalReaction RHEA:17222; this is the selected biosynthetic member. Source location `http://rdf.rhea-db.org/17221 rh:directionalReaction http://rdf.rhea-db.org/17222` MetaCyc:DTDPGLUCDEHYDRAT-CPLX Source assertion: The native dimer catalyzes DTDPGLUCDEHYDRAT-RXN through DTDPGLUCDEHYDRAT-ENZRXN. Source location `Protein[@frameid="DTDPGLUCDEHYDRAT-CPLX"]/catalyzes/Enzymatic-Reaction/reaction`
dTDP-4-dehydrorhamnose 3,5-epimerase `UniProtKB:P37745`	enables The gene-product role combines K-12 mutant/extract evidence and reviewed exact-reaction inference. It does not establish an independently sufficient K-12 monomer or an obligatory RmlC-RmlD complex.	dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose `RHEA:16970`	UniProtKB:P37745 Source assertion: P37745 links RHEA:16969 and C3/C5 epimerization with ECO:0000250 UniProtKB:P26394 (Salmonella); its homodimer annotation has the same inference source. Source location `/comments/0; /comments/1/reaction; /comments/4` RHEA:16970 Source assertion: RHEA:16969 explicitly links directionalReaction RHEA:16970; this is the selected biosynthetic member. Source location `http://rdf.rhea-db.org/16969 rh:directionalReaction http://rdf.rhea-db.org/16970` PMID:10217500 Source assertion: All E. coli strains derive from K-12. BW24599 extracts form free 4-keto-rhamnose, unlike the rmlC deletion mutant BW24970. Purified epimerase experiments in the paper use M. tuberculosis RmlC. Source location `PDF pp.664-668, Table 1, Results, Fig.3 caption and Fig.5`
dTDP-4-dehydrorhamnose reductase `UniProtKB:P37760`	enables This is the probable K-12 RmlD functional assignment, with exact catalysis inferred from Salmonella. The selected NADPH reduction is not evidence that NADH cannot support activity, nor that an isolated monomer is sufficient.	dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	UniProtKB:P37760 Source assertion: P37760 links RHEA:21796 with ECO:0000250 UniProtKB:P26392. Its pathway role is Probable (ECO:0000305 PMID:7517391); NADH/NADPH use and homodimerization are by similarity. Source location `/comments/0; /comments/1/reaction; /comments/5` RHEA:21798 Source assertion: RHEA:21796 explicitly links directionalReaction RHEA:21798; this is the selected biosynthetic member. Source location `http://rdf.rhea-db.org/21796 rh:directionalReaction http://rdf.rhea-db.org/21798` MetaCyc:DTDPRHAMSYN-PWY Source assertion: The native final DTDPDEHYRHAMREDUCT-RXN layout selects R2L from the 4-keto-rhamnose primary compound to dTDP-rhamnose. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-layout[Reaction/@frameid="DTDPDEHYRHAMREDUCT-RXN"]`
Glucose-1-phosphate thymidylyltransferase 1 `UniProtKB:P37744`	part_of The subunit node is not assigned independent catalytic sufficiency.	dTDP-glucose pyrophosphorylase `MetaCyc:CPLX0-8034`	MetaCyc:CPLX0-8034 Source assertion: CPLX0-8034 has 4 copies of DTDPGLUCOSEPP-MONOMER; native species is MG1655, within the selected K-12 scope. Source location `Protein[@frameid="CPLX0-8034"]/component/Protein; component/coefficient; species/Organism` MetaCyc:DTDPGLUCOSEPP-MONOMER Source assertion: DTDPGLUCOSEPP-MONOMER has an explicit UNIPROT P37744 unification cross-reference. Source location `Protein[@frameid="DTDPGLUCOSEPP-MONOMER"]/dblink[dblink-db="UNIPROT"]/dblink-oid; dblink-relationship` UniProtKB:P37744 Source assertion: SUBUNIT specifies a homotetramer with ECO:0000269 PMID:11697907. Source location `/comments/6` PMID:11697907 Source assertion: The indexed primary abstract explicitly describes the E. coli enzyme as homotetrameric. Source location `/resultList/result[id="11697907"]/abstractText`
dTDP-glucose 4,6-dehydratase 1 `UniProtKB:P37759`	part_of The native dimer is corroborated by reviewed similarity annotation; the native 88-kDa experimental citation concerns E. coli B, not a direct K-12 measurement.	dTDP-glucose 4,6-dehydratase 1 `MetaCyc:DTDPGLUCDEHYDRAT-CPLX`	MetaCyc:DTDPGLUCDEHYDRAT-CPLX Source assertion: DTDPGLUCDEHYDRAT-CPLX has 2 copies of DTDPGLUCDEHYDRAT-MONOMER; native species is MG1655, within the selected K-12 scope. Source location `Protein[@frameid="DTDPGLUCDEHYDRAT-CPLX"]/component/Protein; component/coefficient; species/Organism` MetaCyc:DTDPGLUCDEHYDRAT-MONOMER Source assertion: DTDPGLUCDEHYDRAT-MONOMER has an explicit UNIPROT P37759 unification cross-reference. Source location `Protein[@frameid="DTDPGLUCDEHYDRAT-MONOMER"]/dblink[dblink-db="UNIPROT"]/dblink-oid; dblink-relationship` UniProtKB:P37759 Source assertion: SUBUNIT specifies a homodimer with ECO:0000250 UniProtKB:P27830. Source location `/comments/5`
dTDP-glucose pyrophosphorylase `MetaCyc:CPLX0-8034`	has_cofactor Magnesium binding is an explicit experimentally supported annotation, not inferred from an Mg-containing assay mixture.	magnesium(2+) `CHEBI:18420`	UniProtKB:P37744 Source assertion: COFACTOR specifies CHEBI:18420 and one Mg(2+) per subunit with ECO:0000269 PMID:11697907. The inspected primary abstract does not itself specify this cofactor. Source location `/comments/2/cofactors; /comments/2/note`
dTDP-glucose 4,6-dehydratase 1 `MetaCyc:DTDPGLUCDEHYDRAT-CPLX`	has_cofactor Bound NAD cycles internally during oxidation and rereduction, so it is not a net consumed reactant. Binding and stoichiometry are inferred from the RffG paralog.	NAD(1-) `CHEBI:57540`	UniProtKB:P37759 Source assertion: COFACTOR specifies CHEBI:57540 and one NAD(+) per subunit, ECO:0000250 UniProtKB:P27830. FUNCTION describes oxidation, dehydration and reduction. Source location `/comments/2/cofactors; /comments/2/note; /comments/0`
dTDP-4-dehydrorhamnose reductase `UniProtKB:P37760`	has_cofactor The magnesium-binding annotation is inferred from Salmonella RmlD, as is homodimerization; no direct K-12 metal assay or monomeric sufficiency is claimed.	magnesium(2+) `CHEBI:18420`	UniProtKB:P37760 Source assertion: COFACTOR specifies CHEBI:18420 and one Mg(2+) per monomer with ECO:0000250 UniProtKB:P26392. Source location `/comments/2/cofactors; /comments/2/note`
dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	part_of	`GO:0019305`	GO:0019305 Source assertion: GO:0019305 is the non-obsolete biological process for dTDP-rhamnose formation; exact synonyms include dTDP-rhamnose biosynthesis. Source location `/results/0/id; /results/0/name; /results/0/isObsolete; /results/0/definition; /results/0/synonyms` MetaCyc:DTDPRHAMSYN-PWY Source assertion: The complete native dTDP-L-rhamnose route lists DTDPGLUCOSEPP-RXN and selects L2R for this step. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-list; reaction-layout[Reaction/@frameid="DTDPGLUCOSEPP-RXN"]/direction` MetaCyc:DTDPGLUCOSEPP-RXN Source assertion: DTDPGLUCOSEPP-RXN has explicit RHEA 15228 unification cross-reference. Source location `Reaction[@frameid="DTDPGLUCOSEPP-RXN"]/dblink[dblink-db="RHEA"]/dblink-oid; dblink-relationship` RHEA:15226 Source assertion: RHEA:15225 explicitly links bidirectionalReaction RHEA:15228 and directionalReaction RHEA:15226. Source location `http://rdf.rhea-db.org/15225 rh:bidirectionalReaction http://rdf.rhea-db.org/15228; rh:directionalReaction http://rdf.rhea-db.org/15226` UniProtKB:P37744 Source assertion: The reviewed P37744 entry is E. coli K-12 taxon 83333. Its caution states that many K-12 lines fail to express O-antigen because of dTDP-rhamnose biosynthetic or wbbL mutations. Source location `/organism/taxonId; /comments/9` PMID:7517391 Source assertion: The primary K-12 study identifies four rhamnose pathway genes by homology and distinguishes defective laboratory lineages from an engineered strain with intact rfb genes and O16 antigen. Source location `PDF pp.4144,4150; abstract; Results and Discussion, TDP-Rha biosynthetic pathway genes` PMID:10217500 Source assertion: Table 1 identifies all studied E. coli strains as K-12 derivatives. Extracts from repaired-rfb BW24599 synthesize dTDP-rhamnose; rmlC-deletion extracts do not. Source location `PDF pp.664,668; Table 1; Results, dTDP-rha from dTDP-glc`
dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	part_of	`GO:0019305`	GO:0019305 Source assertion: GO:0019305 is the non-obsolete biological process for dTDP-rhamnose formation; exact synonyms include dTDP-rhamnose biosynthesis. Source location `/results/0/id; /results/0/name; /results/0/isObsolete; /results/0/definition; /results/0/synonyms` MetaCyc:DTDPRHAMSYN-PWY Source assertion: The complete native dTDP-L-rhamnose route lists DTDPGLUCDEHYDRAT-RXN and selects L2R for this step. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-list; reaction-layout[Reaction/@frameid="DTDPGLUCDEHYDRAT-RXN"]/direction` MetaCyc:DTDPGLUCDEHYDRAT-RXN Source assertion: DTDPGLUCDEHYDRAT-RXN has explicit RHEA 17221 unification cross-reference. Source location `Reaction[@frameid="DTDPGLUCDEHYDRAT-RXN"]/dblink[dblink-db="RHEA"]/dblink-oid; dblink-relationship` RHEA:17222 Source assertion: RHEA:17221 explicitly links directionalReaction RHEA:17222; this is the selected biosynthetic member. Source location `http://rdf.rhea-db.org/17221 rh:directionalReaction http://rdf.rhea-db.org/17222`
dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose `RHEA:16970`	part_of	`GO:0019305`	GO:0019305 Source assertion: GO:0019305 is the non-obsolete biological process for dTDP-rhamnose formation; exact synonyms include dTDP-rhamnose biosynthesis. Source location `/results/0/id; /results/0/name; /results/0/isObsolete; /results/0/definition; /results/0/synonyms` MetaCyc:DTDPRHAMSYN-PWY Source assertion: The complete native dTDP-L-rhamnose route lists DTDPDEHYDRHAMEPIM-RXN and selects L2R for this step. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-list; reaction-layout[Reaction/@frameid="DTDPDEHYDRHAMEPIM-RXN"]/direction` MetaCyc:DTDPDEHYDRHAMEPIM-RXN Source assertion: DTDPDEHYDRHAMEPIM-RXN has explicit RHEA 16969 unification cross-reference. Source location `Reaction[@frameid="DTDPDEHYDRHAMEPIM-RXN"]/dblink[dblink-db="RHEA"]/dblink-oid; dblink-relationship` RHEA:16970 Source assertion: RHEA:16969 explicitly links directionalReaction RHEA:16970; this is the selected biosynthetic member. Source location `http://rdf.rhea-db.org/16969 rh:directionalReaction http://rdf.rhea-db.org/16970`
dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	part_of	`GO:0019305`	GO:0019305 Source assertion: GO:0019305 is the non-obsolete biological process for dTDP-rhamnose formation; exact synonyms include dTDP-rhamnose biosynthesis. Source location `/results/0/id; /results/0/name; /results/0/isObsolete; /results/0/definition; /results/0/synonyms` MetaCyc:DTDPRHAMSYN-PWY Source assertion: The complete native dTDP-L-rhamnose route lists DTDPDEHYRHAMREDUCT-RXN and selects R2L for this step. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-list; reaction-layout[Reaction/@frameid="DTDPDEHYRHAMREDUCT-RXN"]/direction` MetaCyc:DTDPDEHYRHAMREDUCT-RXN Source assertion: DTDPDEHYRHAMREDUCT-RXN has explicit RHEA 21796 unification cross-reference. Source location `Reaction[@frameid="DTDPDEHYRHAMREDUCT-RXN"]/dblink[dblink-db="RHEA"]/dblink-oid; dblink-relationship` RHEA:21798 Source assertion: RHEA:21796 explicitly links directionalReaction RHEA:21798; this is the selected biosynthetic member. Source location `http://rdf.rhea-db.org/21796 rh:directionalReaction http://rdf.rhea-db.org/21798`
dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate `RHEA:15226`	provides_input_for The shared intermediate connects the complete native pathway in the selected biosynthetic direction.	dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	MetaCyc:DTDPRHAMSYN-PWY Source assertion: DTDPGLUCDEHYDRAT-RXN explicitly follows DTDPGLUCOSEPP-RXN in the native route. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-ordering[Reaction/@frameid="DTDPGLUCDEHYDRAT-RXN"]` RHEA:15226 Source assertion: RHEA:15226 produces CHEBI:57477, the intermediate consumed by the next selected reaction. Source location `http://rdf.rhea-db.org/15226 rh:products; http://rdf.rhea-db.org/15225_R rh:contains1` RHEA:17222 Source assertion: RHEA:17222 consumes the chemically identical CHEBI:57477. Source location `http://rdf.rhea-db.org/17222 rh:substrates; http://rdf.rhea-db.org/17221_L rh:contains1`
dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O `RHEA:17222`	provides_input_for The shared intermediate connects the complete native pathway in the selected biosynthetic direction.	dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose `RHEA:16970`	MetaCyc:DTDPRHAMSYN-PWY Source assertion: DTDPDEHYDRHAMEPIM-RXN explicitly follows DTDPGLUCDEHYDRAT-RXN in the native route. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-ordering[Reaction/@frameid="DTDPDEHYDRHAMEPIM-RXN"]` RHEA:17222 Source assertion: RHEA:17222 produces CHEBI:57649, the intermediate consumed by the next selected reaction. Source location `http://rdf.rhea-db.org/17222 rh:products; http://rdf.rhea-db.org/17221_R rh:contains1` RHEA:16970 Source assertion: RHEA:16970 consumes the chemically identical CHEBI:57649. Source location `http://rdf.rhea-db.org/16970 rh:substrates; http://rdf.rhea-db.org/16969_L rh:contains1`
dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose `RHEA:16970`	provides_input_for The intermediate is free rather than obligatorily channeled through a joint RmlC-RmlD complex. The native monomer prose asserting unreleased intermediate is not adopted; the cited primary paper demonstrates release.	dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) `RHEA:21798`	MetaCyc:DTDPRHAMSYN-PWY Source assertion: DTDPDEHYRHAMREDUCT-RXN explicitly follows DTDPDEHYDRHAMEPIM-RXN in the native route. Source location `Pathway[@frameid="DTDPRHAMSYN-PWY"]/reaction-ordering[Reaction/@frameid="DTDPDEHYRHAMREDUCT-RXN"]` RHEA:16970 Source assertion: RHEA:16970 produces CHEBI:62830, the intermediate consumed by the next selected reaction. Source location `http://rdf.rhea-db.org/16970 rh:products; http://rdf.rhea-db.org/16969_R rh:contains1` RHEA:21798 Source assertion: RHEA:21798 consumes the chemically identical CHEBI:62830. Source location `http://rdf.rhea-db.org/21798 rh:substrates; http://rdf.rhea-db.org/21796_R rh:contains1` PMID:10217500 Source assertion: K-12 extract experiments show free 4-keto-rhamnose; the Discussion concludes epimerase can function independently of reductase, while not excluding possible in vivo interaction. Source location `PDF pp.664,667-669; Fig.3 caption; Discussion final paragraphs`

References

GO:0019305 Gene Ontology dTDP-rhamnose biosynthetic process (source version: QuickGO term response retrieved 2026-10-11 UTC)
MetaCyc:DTDPRHAMSYN-PWY dTDP-L-rhamnose biosynthesis: complete native four-step boundary (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
MetaCyc:DTDPGLUCOSEPP-RXN Native DTDPGLUCOSEPP-RXN reaction and cross-references (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
RHEA:15226 dTTP + alpha-D-glucose 1-phosphate + H(+) => dTDP-alpha-D-glucose + diphosphate (source version: Rhea 142, released 2026-09-02; digest covers the complete compressed RDF source)
UniProtKB:P37744 Reviewed E. coli K-12 Glucose-1-phosphate thymidylyltransferase 1 (source version: UniProt 2026_03; complete JSON entry retrieved 2026-10-11 UTC)
MetaCyc:DTDPGLUCDEHYDRAT-RXN Native DTDPGLUCDEHYDRAT-RXN reaction and cross-references (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
RHEA:17222 dTDP-alpha-D-glucose => dTDP-4-dehydro-6-deoxy-alpha-D-glucose + H2O (source version: Rhea 142, released 2026-09-02; digest covers the complete compressed RDF source)
UniProtKB:P37759 Reviewed E. coli K-12 dTDP-glucose 4,6-dehydratase 1 (source version: UniProt 2026_03; complete JSON entry retrieved 2026-10-11 UTC)
MetaCyc:DTDPDEHYDRHAMEPIM-RXN Native DTDPDEHYDRHAMEPIM-RXN reaction and cross-references (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
RHEA:16970 dTDP-4-dehydro-6-deoxy-alpha-D-glucose => dTDP-4-dehydro-beta-L-rhamnose (source version: Rhea 142, released 2026-09-02; digest covers the complete compressed RDF source)
UniProtKB:P37745 Reviewed E. coli K-12 dTDP-4-dehydrorhamnose 3,5-epimerase (source version: UniProt 2026_03; complete JSON entry retrieved 2026-10-11 UTC)
MetaCyc:DTDPDEHYRHAMREDUCT-RXN Native DTDPDEHYRHAMREDUCT-RXN reaction and cross-references (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
RHEA:21798 dTDP-4-dehydro-beta-L-rhamnose + NADPH + H(+) => dTDP-beta-L-rhamnose + NADP(+) (source version: Rhea 142, released 2026-09-02; digest covers the complete compressed RDF source)
UniProtKB:P37760 Reviewed E. coli K-12 dTDP-4-dehydrorhamnose reductase (source version: UniProt 2026_03; complete JSON entry retrieved 2026-10-11 UTC)
MetaCyc:CPLX0-8034 Native RmlA/RmlB protein identity and assembly: CPLX0-8034 (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
MetaCyc:DTDPGLUCOSEPP-MONOMER Native RmlA/RmlB protein identity and assembly: DTDPGLUCOSEPP-MONOMER (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
MetaCyc:DTDPGLUCDEHYDRAT-CPLX Native RmlA/RmlB protein identity and assembly: DTDPGLUCDEHYDRAT-CPLX (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
MetaCyc:DTDPGLUCDEHYDRAT-MONOMER Native RmlA/RmlB protein identity and assembly: DTDPGLUCDEHYDRAT-MONOMER (source version: MetaCyc 22.5; full native XML body retrieved 2026-10-11 UTC)
PMID:11697907 Kinetic and crystallographic analyses support a sequential-ordered bi bi catalytic mechanism for Escherichia coli glucose-1-phosphate thymidylyltransferase. (source version: Indexed abstract in Europe PMC core JSON; full publisher article was not accessible; retrieved 2026-10-11 UTC)
PMID:7517391 Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb gene cluster. (source version: Complete primary PDF; pages 4144-4156; retrieved 2026-10-11 UTC)
PMID:10217500 Conversion of dTDP-4-keto-6-deoxyglucose to free dTDP-4-keto-rhamnose by the rmIC gene products of Escherichia coli and Mycobacterium tuberculosis. (source version: Complete primary publisher PDF; pages 663-671; retrieved 2026-10-11 UTC)

Curation history

2026-10-11T03:53:22Z Codex
- CREATE — Add the complete dTDP-rhamnose biosynthetic pathway.
  Retained all four native steps and current Rhea chemistry, preserving similarity-based enzyme assignments and rejecting unsupported intermediate channeling. Source dossiers and verification receipts are in research/pathway_additions/2026-10-11-next-186; independent scientific assessments are saved separately.
Read this curation session