superpathway of thiamine diphosphate biosynthesis I

MetaCyc:THISYN-PWY

The complete native MetaCyc de novo route is represented for the Escherichia coli K-12 protein core: AIR-to-HMP-PP synthesis, cysteine-derived sulfur transfer and DXP/tyrosine-dependent thiazole synthesis, then ThiE coupling and ThiL phosphorylation to thiamine diphosphate. Its three children contain eleven native reactions; current Rhea net sulfur transfer replaces two native ThiI relay steps, yielding ten nonduplicated reactions. All five sulfur-carrier states are whole proteins. The net reductant AH2/A remains generic, and the graph does not assert a specific ferredoxin or an elementary ThiI/ThiF disulfide sequence. ThiI stimulation in reconstitution is preserved without universal indispensability. ThiGH is a heterodimeric unit isolated also as larger multimers; its native six-plus-six assembly is qualified by experiment. ThiC cluster/oligomer and ThiE magnesium assignments retain their inference grades; ThiD oligomer annotations differ between sources. Exact thiazole tautomer chemistry follows current curated annotation, with Bacillus product-structure studies kept distinct from E. coli assays. Dxs requires the pathway product as a cofactor. PurF/D/N-or-T/L/M steps in the initial PathBank lead are upstream of this native AIR boundary; they are not omitted branches of THISYN-PWY. Thiamine salvage, TenI/ThiO variants, tRNA thiolation, Fe-S assembly, downstream cofactor utilization and engineered bypasses are outside this record. This reaction-level graph does not claim every transient intermediate is resolved, uniform wild-type flux, or complete elementary enzymology.

Pathway type

cofactor biosynthesis

Organism scope

Escherichia coli K-12 NCBITaxon:83333

Read the source YAML

Pathway network

64 nodes · 92 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

Find a node

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

Show at full size (scroll to explore)

Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli K-12 `NCBITaxon:83333`	taxon
Phosphomethylpyrimidine synthase `UniProtKB:P30136`	protein
Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase `UniProtKB:P76422`	protein
Thiamine-phosphate synthase `UniProtKB:P30137`	protein
Thiamine-monophosphate kinase `UniProtKB:P0AGG0`	protein
Sulfur carrier protein ThiS adenylyltransferase `UniProtKB:P30138`	protein
Thiazole synthase `UniProtKB:P30139`	protein
2-iminoacetate synthase `UniProtKB:P30140`	protein
tRNA sulfurtransferase `UniProtKB:P77718`	protein
1-deoxy-D-xylulose-5-phosphate synthase `UniProtKB:P77488`	protein
Cysteine desulfurase IscS `UniProtKB:P0A6B7`	protein
Sulfur carrier protein ThiS `UniProtKB:O32583`	protein
cysteine desulfurase `MetaCyc:CPLX0-248`	complex
1-deoxy-D-xylulose-5-phosphate synthase `MetaCyc:CPLX0-743`	complex
thiazole synthase `MetaCyc:CPLX0-3949`	complex
hydrogen acceptor `CHEBI:13193`	small molecule
5-amino-1-(5-phosphonato-beta-D-ribosyl)imidazol-3-ium `CHEBI:137981`	small molecule
pyruvate `CHEBI:15361`	small molecule
water `CHEBI:15377`	small molecule
hydron `CHEBI:15378`	small molecule
formate `CHEBI:15740`	small molecule
carbon dioxide `CHEBI:16526`	small molecule
carbon monoxide `CHEBI:17245`	small molecule
5'-deoxyadenosine `CHEBI:17319`	small molecule
hydrogen donor `CHEBI:17499`	small molecule
p-cresol `CHEBI:17847`	small molecule
magnesium(2+) `CHEBI:18420`	cofactor
zinc(2+) `CHEBI:29105`	cofactor
ATP(4-) `CHEBI:30616`	small molecule
diphosphate(3-) `CHEBI:33019`	small molecule
L-cysteine zwitterion `CHEBI:35235`	small molecule
thiamine(1+) monophosphate(2-) `CHEBI:37575`	small molecule
adenosine 5'-monophosphate(2-) `CHEBI:456215`	small molecule
ADP(3-) `CHEBI:456216`	small molecule
tetra-mu3-sulfido-tetrairon `CHEBI:49883`	cofactor
NADPH(4-) `CHEBI:57783`	small molecule
1-deoxy-D-xylulose 5-phosphate(2-) `CHEBI:57792`	small molecule
4-amino-2-methyl-5-diphosphonatooxymethylpyrimidine(3-) `CHEBI:57841`	small molecule
L-methionine zwitterion `CHEBI:57844`	small molecule
L-alanine zwitterion `CHEBI:57972`	small molecule
L-tyrosine zwitterion `CHEBI:58315`	small molecule
NADP(3-) `CHEBI:58349`	small molecule
4-amino-2-methyl-5-phosphonatooxymethylpyrimidine(2-) `CHEBI:58354`	small molecule
thiamine(1+) diphosphate(3-) `CHEBI:58937`	cofactor
pyridoxal 5'-phosphate(2-) `CHEBI:597326`	cofactor
D-glyceraldehyde 3-phosphate(2-) `CHEBI:59776`	small molecule
S-adenosyl-L-methionine zwitterion `CHEBI:59789`	small molecule
(R,Z)- 2-carboxylato-4-methyl-5-[(2-phosphonatooxy)ethylidene]-2,5-dihydrothiazole(3-) `CHEBI:62899`	small molecule
dehydroglycine zwitterion `CHEBI:77846`	small molecule
S-sulfanyl-L-cysteinyl-[cysteine desulfurase] `RHEA-COMP:12157`	protein
L-cysteinyl-[cysteine desulfurase] `RHEA-COMP:12158`	protein
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly `RHEA-COMP:12909`	protein
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP `RHEA-COMP:12910`	protein
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate `RHEA-COMP:19908`	protein
L-cysteinyl-[cysteine desulfurase] + L-cysteine => S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + L-alanine `RHEA:17458`	molecular activity	left to right
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	molecular activity	left to right
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	molecular activity	left to right
D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	molecular activity	left to right
L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	molecular activity	left to right
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	molecular activity	left to right
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	molecular activity	left to right
4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP => 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP `RHEA:19894`	molecular activity	left to right
2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	molecular activity	left to right
thiamine phosphate + ATP => thiamine diphosphate + ADP `RHEA:15914`	molecular activity	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
L-cysteinyl-[cysteine desulfurase] `RHEA-COMP:12158`	consumes Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	L-cysteinyl-[cysteine desulfurase] + L-cysteine => S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + L-alanine `RHEA:17458`	RHEA:17457 Source assertion: RHEA:17458 substrates contain RHEA-COMP:12158 with coefficient 1. Source location `http://rdf.rhea-db.org/17458 rh:substrates; http://rdf.rhea-db.org/17457_L rh:contains1 http://rdf.rhea-db.org/Participant_17457_compound_12158; rh:compound http://rdf.rhea-db.org/Compound_12158`
L-cysteine zwitterion `CHEBI:35235`	consumes Coefficient 1 in the selected biosynthetic direction.	L-cysteinyl-[cysteine desulfurase] + L-cysteine => S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + L-alanine `RHEA:17458`	RHEA:17457 Source assertion: RHEA:17458 substrates contain CHEBI:35235 with coefficient 1. Source location `http://rdf.rhea-db.org/17458 rh:substrates; http://rdf.rhea-db.org/17457_L rh:contains1 http://rdf.rhea-db.org/Participant_17457_compound_2467; rh:compound http://rdf.rhea-db.org/Compound_2467`
L-cysteinyl-[cysteine desulfurase] + L-cysteine => S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + L-alanine `RHEA:17458`	produces Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	S-sulfanyl-L-cysteinyl-[cysteine desulfurase] `RHEA-COMP:12157`	RHEA:17457 Source assertion: RHEA:17458 products contain RHEA-COMP:12157 with coefficient 1. Source location `http://rdf.rhea-db.org/17458 rh:products; http://rdf.rhea-db.org/17457_R rh:contains1 http://rdf.rhea-db.org/Participant_17457_compound_12157; rh:compound http://rdf.rhea-db.org/Compound_12157`
L-cysteinyl-[cysteine desulfurase] + L-cysteine => S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + L-alanine `RHEA:17458`	produces Coefficient 1 in the selected biosynthetic direction.	L-alanine zwitterion `CHEBI:57972`	RHEA:17457 Source assertion: RHEA:17458 products contain CHEBI:57972 with coefficient 1. Source location `http://rdf.rhea-db.org/17458 rh:products; http://rdf.rhea-db.org/17457_R rh:contains1 http://rdf.rhea-db.org/Participant_17457_compound_3361; rh:compound http://rdf.rhea-db.org/Compound_3361`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly `RHEA-COMP:12909`	consumes Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	RHEA:43344 Source assertion: RHEA:43345 substrates contain RHEA-COMP:12909 with coefficient 1. Source location `http://rdf.rhea-db.org/43345 rh:substrates; http://rdf.rhea-db.org/43344_L rh:contains1 http://rdf.rhea-db.org/Participant_43344_compound_12909; rh:compound http://rdf.rhea-db.org/Compound_12909`
ATP(4-) `CHEBI:30616`	consumes Coefficient 1 in the selected biosynthetic direction.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	RHEA:43344 Source assertion: RHEA:43345 substrates contain CHEBI:30616 with coefficient 1. Source location `http://rdf.rhea-db.org/43345 rh:substrates; http://rdf.rhea-db.org/43344_L rh:contains1 http://rdf.rhea-db.org/Participant_43344_compound_6372; rh:compound http://rdf.rhea-db.org/Compound_6372`
hydron `CHEBI:15378`	consumes Coefficient 1 in the selected biosynthetic direction.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	RHEA:43344 Source assertion: RHEA:43345 substrates contain CHEBI:15378 with coefficient 1. Source location `http://rdf.rhea-db.org/43345 rh:substrates; http://rdf.rhea-db.org/43344_L rh:contains1 http://rdf.rhea-db.org/Participant_43344_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	produces Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP `RHEA-COMP:12910`	RHEA:43344 Source assertion: RHEA:43345 products contain RHEA-COMP:12910 with coefficient 1. Source location `http://rdf.rhea-db.org/43345 rh:products; http://rdf.rhea-db.org/43344_R rh:contains1 http://rdf.rhea-db.org/Participant_43344_compound_12910; rh:compound http://rdf.rhea-db.org/Compound_12910`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	produces Coefficient 1 in the selected biosynthetic direction.	diphosphate(3-) `CHEBI:33019`	RHEA:43344 Source assertion: RHEA:43345 products contain CHEBI:33019 with coefficient 1. Source location `http://rdf.rhea-db.org/43345 rh:products; http://rdf.rhea-db.org/43344_R rh:contains1 http://rdf.rhea-db.org/Participant_43344_compound_2106; rh:compound http://rdf.rhea-db.org/Compound_2106`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP `RHEA-COMP:12910`	consumes Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	RHEA:43340 Source assertion: RHEA:43341 substrates contain RHEA-COMP:12910 with coefficient 1. Source location `http://rdf.rhea-db.org/43341 rh:substrates; http://rdf.rhea-db.org/43340_L rh:contains1 http://rdf.rhea-db.org/Participant_43340_compound_12910; rh:compound http://rdf.rhea-db.org/Compound_12910`
S-sulfanyl-L-cysteinyl-[cysteine desulfurase] `RHEA-COMP:12157`	consumes Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	RHEA:43340 Source assertion: RHEA:43341 substrates contain RHEA-COMP:12157 with coefficient 1. Source location `http://rdf.rhea-db.org/43341 rh:substrates; http://rdf.rhea-db.org/43340_L rh:contains1 http://rdf.rhea-db.org/Participant_43340_compound_12157; rh:compound http://rdf.rhea-db.org/Compound_12157`
hydrogen donor `CHEBI:17499`	consumes Coefficient 1 in the selected biosynthetic direction. AH2/A are generic donor/acceptor classes, not an identified physiological reductant.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	RHEA:43340 Source assertion: RHEA:43341 substrates contain CHEBI:17499 with coefficient 1. Source location `http://rdf.rhea-db.org/43341 rh:substrates; http://rdf.rhea-db.org/43340_L rh:contains1 http://rdf.rhea-db.org/Participant_43340_compound_1304; rh:compound http://rdf.rhea-db.org/Compound_1304`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	produces Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate `RHEA-COMP:19908`	RHEA:43340 Source assertion: RHEA:43341 products contain RHEA-COMP:19908 with coefficient 1. Source location `http://rdf.rhea-db.org/43341 rh:products; http://rdf.rhea-db.org/43340_R rh:contains1 http://rdf.rhea-db.org/Participant_43340_compound_19908; rh:compound http://rdf.rhea-db.org/Compound_19908`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	produces Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	L-cysteinyl-[cysteine desulfurase] `RHEA-COMP:12158`	RHEA:43340 Source assertion: RHEA:43341 products contain RHEA-COMP:12158 with coefficient 1. Source location `http://rdf.rhea-db.org/43341 rh:products; http://rdf.rhea-db.org/43340_R rh:contains1 http://rdf.rhea-db.org/Participant_43340_compound_12158; rh:compound http://rdf.rhea-db.org/Compound_12158`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	produces Coefficient 1 in the selected biosynthetic direction. AH2/A are generic donor/acceptor classes, not an identified physiological reductant.	hydrogen acceptor `CHEBI:13193`	RHEA:43340 Source assertion: RHEA:43341 products contain CHEBI:13193 with coefficient 1. Source location `http://rdf.rhea-db.org/43341 rh:products; http://rdf.rhea-db.org/43340_R rh:contains1 http://rdf.rhea-db.org/Participant_43340_compound_3512; rh:compound http://rdf.rhea-db.org/Compound_3512`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	produces Coefficient 1 in the selected biosynthetic direction.	adenosine 5'-monophosphate(2-) `CHEBI:456215`	RHEA:43340 Source assertion: RHEA:43341 products contain CHEBI:456215 with coefficient 1. Source location `http://rdf.rhea-db.org/43341 rh:products; http://rdf.rhea-db.org/43340_R rh:contains1 http://rdf.rhea-db.org/Participant_43340_compound_2590; rh:compound http://rdf.rhea-db.org/Compound_2590`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	produces Coefficient 2 in the selected biosynthetic direction.	hydron `CHEBI:15378`	RHEA:43340 Source assertion: RHEA:43341 products contain CHEBI:15378 with coefficient 2. Source location `http://rdf.rhea-db.org/43341 rh:products; http://rdf.rhea-db.org/43340_R rh:contains2 http://rdf.rhea-db.org/Participant_43340_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
D-glyceraldehyde 3-phosphate(2-) `CHEBI:59776`	consumes Coefficient 1 in the selected biosynthetic direction.	D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	RHEA:12605 Source assertion: RHEA:12606 substrates contain CHEBI:59776 with coefficient 1. Source location `http://rdf.rhea-db.org/12606 rh:substrates; http://rdf.rhea-db.org/12605_L rh:contains1 http://rdf.rhea-db.org/Participant_12605_compound_6062; rh:compound http://rdf.rhea-db.org/Compound_6062`
pyruvate `CHEBI:15361`	consumes Coefficient 1 in the selected biosynthetic direction.	D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	RHEA:12605 Source assertion: RHEA:12606 substrates contain CHEBI:15361 with coefficient 1. Source location `http://rdf.rhea-db.org/12606 rh:substrates; http://rdf.rhea-db.org/12605_L rh:contains1 http://rdf.rhea-db.org/Participant_12605_compound_3719; rh:compound http://rdf.rhea-db.org/Compound_3719`
hydron `CHEBI:15378`	consumes Coefficient 1 in the selected biosynthetic direction.	D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	RHEA:12605 Source assertion: RHEA:12606 substrates contain CHEBI:15378 with coefficient 1. Source location `http://rdf.rhea-db.org/12606 rh:substrates; http://rdf.rhea-db.org/12605_L rh:contains1 http://rdf.rhea-db.org/Participant_12605_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	produces Coefficient 1 in the selected biosynthetic direction.	1-deoxy-D-xylulose 5-phosphate(2-) `CHEBI:57792`	RHEA:12605 Source assertion: RHEA:12606 products contain CHEBI:57792 with coefficient 1. Source location `http://rdf.rhea-db.org/12606 rh:products; http://rdf.rhea-db.org/12605_R rh:contains1 http://rdf.rhea-db.org/Participant_12605_compound_2654; rh:compound http://rdf.rhea-db.org/Compound_2654`
D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	produces Coefficient 1 in the selected biosynthetic direction.	carbon dioxide `CHEBI:16526`	RHEA:12605 Source assertion: RHEA:12606 products contain CHEBI:16526 with coefficient 1. Source location `http://rdf.rhea-db.org/12606 rh:products; http://rdf.rhea-db.org/12605_R rh:contains1 http://rdf.rhea-db.org/Participant_12605_compound_4391; rh:compound http://rdf.rhea-db.org/Compound_4391`
L-tyrosine zwitterion `CHEBI:58315`	consumes Coefficient 1 in the selected biosynthetic direction.	L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	RHEA:26361 Source assertion: RHEA:26362 substrates contain CHEBI:58315 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:substrates; http://rdf.rhea-db.org/26361_L rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_1046; rh:compound http://rdf.rhea-db.org/Compound_1046`
S-adenosyl-L-methionine zwitterion `CHEBI:59789`	consumes Coefficient 1 in the selected biosynthetic direction.	L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	RHEA:26361 Source assertion: RHEA:26362 substrates contain CHEBI:59789 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:substrates; http://rdf.rhea-db.org/26361_L rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_6127; rh:compound http://rdf.rhea-db.org/Compound_6127`
NADPH(4-) `CHEBI:57783`	consumes Coefficient 1 in the selected biosynthetic direction.	L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	RHEA:26361 Source assertion: RHEA:26362 substrates contain CHEBI:57783 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:substrates; http://rdf.rhea-db.org/26361_L rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_3438; rh:compound http://rdf.rhea-db.org/Compound_3438`
L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	produces Coefficient 1 in the selected biosynthetic direction.	dehydroglycine zwitterion `CHEBI:77846`	RHEA:26361 Source assertion: RHEA:26362 products contain CHEBI:77846 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:products; http://rdf.rhea-db.org/26361_R rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_9982; rh:compound http://rdf.rhea-db.org/Compound_9982`
L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	produces Coefficient 1 in the selected biosynthetic direction.	p-cresol `CHEBI:17847`	RHEA:26361 Source assertion: RHEA:26362 products contain CHEBI:17847 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:products; http://rdf.rhea-db.org/26361_R rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_4232; rh:compound http://rdf.rhea-db.org/Compound_4232`
L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	produces Coefficient 1 in the selected biosynthetic direction.	5'-deoxyadenosine `CHEBI:17319`	RHEA:26361 Source assertion: RHEA:26362 products contain CHEBI:17319 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:products; http://rdf.rhea-db.org/26361_R rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_2028; rh:compound http://rdf.rhea-db.org/Compound_2028`
L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	produces Coefficient 1 in the selected biosynthetic direction.	L-methionine zwitterion `CHEBI:57844`	RHEA:26361 Source assertion: RHEA:26362 products contain CHEBI:57844 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:products; http://rdf.rhea-db.org/26361_R rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_2530; rh:compound http://rdf.rhea-db.org/Compound_2530`
L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	produces Coefficient 1 in the selected biosynthetic direction.	NADP(3-) `CHEBI:58349`	RHEA:26361 Source assertion: RHEA:26362 products contain CHEBI:58349 with coefficient 1. Source location `http://rdf.rhea-db.org/26362 rh:products; http://rdf.rhea-db.org/26361_R rh:contains1 http://rdf.rhea-db.org/Participant_26361_compound_5188; rh:compound http://rdf.rhea-db.org/Compound_5188`
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate `RHEA-COMP:19908`	consumes Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	RHEA:26297 Source assertion: RHEA:26298 substrates contain RHEA-COMP:19908 with coefficient 1. Source location `http://rdf.rhea-db.org/26298 rh:substrates; http://rdf.rhea-db.org/26297_L rh:contains1 http://rdf.rhea-db.org/Participant_26297_compound_19908; rh:compound http://rdf.rhea-db.org/Compound_19908`
dehydroglycine zwitterion `CHEBI:77846`	consumes Coefficient 1 in the selected biosynthetic direction.	[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	RHEA:26297 Source assertion: RHEA:26298 substrates contain CHEBI:77846 with coefficient 1. Source location `http://rdf.rhea-db.org/26298 rh:substrates; http://rdf.rhea-db.org/26297_L rh:contains1 http://rdf.rhea-db.org/Participant_26297_compound_9982; rh:compound http://rdf.rhea-db.org/Compound_9982`
1-deoxy-D-xylulose 5-phosphate(2-) `CHEBI:57792`	consumes Coefficient 1 in the selected biosynthetic direction.	[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	RHEA:26297 Source assertion: RHEA:26298 substrates contain CHEBI:57792 with coefficient 1. Source location `http://rdf.rhea-db.org/26298 rh:substrates; http://rdf.rhea-db.org/26297_L rh:contains1 http://rdf.rhea-db.org/Participant_26297_compound_2654; rh:compound http://rdf.rhea-db.org/Compound_2654`
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	produces Coefficient 1 in the selected biosynthetic direction. Whole protein carrier state is retained; the reactive ChEBI residue is not substituted for the protein.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly `RHEA-COMP:12909`	RHEA:26297 Source assertion: RHEA:26298 products contain RHEA-COMP:12909 with coefficient 1. Source location `http://rdf.rhea-db.org/26298 rh:products; http://rdf.rhea-db.org/26297_R rh:contains1 http://rdf.rhea-db.org/Participant_26297_compound_12909; rh:compound http://rdf.rhea-db.org/Compound_12909`
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	produces Coefficient 1 in the selected biosynthetic direction.	(R,Z)- 2-carboxylato-4-methyl-5-[(2-phosphonatooxy)ethylidene]-2,5-dihydrothiazole(3-) `CHEBI:62899`	RHEA:26297 Source assertion: RHEA:26298 products contain CHEBI:62899 with coefficient 1. Source location `http://rdf.rhea-db.org/26298 rh:products; http://rdf.rhea-db.org/26297_R rh:contains1 http://rdf.rhea-db.org/Participant_26297_compound_6833; rh:compound http://rdf.rhea-db.org/Compound_6833`
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	produces Coefficient 1 in the selected biosynthetic direction.	hydron `CHEBI:15378`	RHEA:26297 Source assertion: RHEA:26298 products contain CHEBI:15378 with coefficient 1. Source location `http://rdf.rhea-db.org/26298 rh:products; http://rdf.rhea-db.org/26297_R rh:contains1 http://rdf.rhea-db.org/Participant_26297_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	produces Coefficient 2 in the selected biosynthetic direction.	water `CHEBI:15377`	RHEA:26297 Source assertion: RHEA:26298 products contain CHEBI:15377 with coefficient 2. Source location `http://rdf.rhea-db.org/26298 rh:products; http://rdf.rhea-db.org/26297_R rh:contains2 http://rdf.rhea-db.org/Participant_26297_compound_1283; rh:compound http://rdf.rhea-db.org/Compound_1283`
5-amino-1-(5-phosphonato-beta-D-ribosyl)imidazol-3-ium `CHEBI:137981`	consumes Coefficient 1 in the selected biosynthetic direction.	5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	RHEA:24840 Source assertion: RHEA:24841 substrates contain CHEBI:137981 with coefficient 1. Source location `http://rdf.rhea-db.org/24841 rh:substrates; http://rdf.rhea-db.org/24840_L rh:contains1 http://rdf.rhea-db.org/Participant_24840_compound_13720; rh:compound http://rdf.rhea-db.org/Compound_13720`
S-adenosyl-L-methionine zwitterion `CHEBI:59789`	consumes Coefficient 1 in the selected biosynthetic direction.	5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	RHEA:24840 Source assertion: RHEA:24841 substrates contain CHEBI:59789 with coefficient 1. Source location `http://rdf.rhea-db.org/24841 rh:substrates; http://rdf.rhea-db.org/24840_L rh:contains1 http://rdf.rhea-db.org/Participant_24840_compound_6127; rh:compound http://rdf.rhea-db.org/Compound_6127`
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	produces Coefficient 1 in the selected biosynthetic direction.	4-amino-2-methyl-5-phosphonatooxymethylpyrimidine(2-) `CHEBI:58354`	RHEA:24840 Source assertion: RHEA:24841 products contain CHEBI:58354 with coefficient 1. Source location `http://rdf.rhea-db.org/24841 rh:products; http://rdf.rhea-db.org/24840_R rh:contains1 http://rdf.rhea-db.org/Participant_24840_compound_1332; rh:compound http://rdf.rhea-db.org/Compound_1332`
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	produces Coefficient 1 in the selected biosynthetic direction.	carbon monoxide `CHEBI:17245`	RHEA:24840 Source assertion: RHEA:24841 products contain CHEBI:17245 with coefficient 1. Source location `http://rdf.rhea-db.org/24841 rh:products; http://rdf.rhea-db.org/24840_R rh:contains1 http://rdf.rhea-db.org/Participant_24840_compound_7041; rh:compound http://rdf.rhea-db.org/Compound_7041`
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	produces Coefficient 1 in the selected biosynthetic direction.	5'-deoxyadenosine `CHEBI:17319`	RHEA:24840 Source assertion: RHEA:24841 products contain CHEBI:17319 with coefficient 1. Source location `http://rdf.rhea-db.org/24841 rh:products; http://rdf.rhea-db.org/24840_R rh:contains1 http://rdf.rhea-db.org/Participant_24840_compound_2028; rh:compound http://rdf.rhea-db.org/Compound_2028`
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	produces Coefficient 1 in the selected biosynthetic direction.	formate `CHEBI:15740`	RHEA:24840 Source assertion: RHEA:24841 products contain CHEBI:15740 with coefficient 1. Source location `http://rdf.rhea-db.org/24841 rh:products; http://rdf.rhea-db.org/24840_R rh:contains1 http://rdf.rhea-db.org/Participant_24840_compound_3001; rh:compound http://rdf.rhea-db.org/Compound_3001`
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	produces Coefficient 1 in the selected biosynthetic direction.	L-methionine zwitterion `CHEBI:57844`	RHEA:24840 Source assertion: RHEA:24841 products contain CHEBI:57844 with coefficient 1. Source location `http://rdf.rhea-db.org/24841 rh:products; http://rdf.rhea-db.org/24840_R rh:contains1 http://rdf.rhea-db.org/Participant_24840_compound_2530; rh:compound http://rdf.rhea-db.org/Compound_2530`
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	produces Coefficient 3 in the selected biosynthetic direction.	hydron `CHEBI:15378`	RHEA:24840 Source assertion: RHEA:24841 products contain CHEBI:15378 with coefficient 3. Source location `http://rdf.rhea-db.org/24841 rh:products; http://rdf.rhea-db.org/24840_R rh:contains3 http://rdf.rhea-db.org/Participant_24840_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
4-amino-2-methyl-5-phosphonatooxymethylpyrimidine(2-) `CHEBI:58354`	consumes Coefficient 1 in the selected biosynthetic direction.	4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP => 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP `RHEA:19894`	RHEA:19893 Source assertion: RHEA:19894 substrates contain CHEBI:58354 with coefficient 1. Source location `http://rdf.rhea-db.org/19894 rh:substrates; http://rdf.rhea-db.org/19893_L rh:contains1 http://rdf.rhea-db.org/Participant_19893_compound_1332; rh:compound http://rdf.rhea-db.org/Compound_1332`
ATP(4-) `CHEBI:30616`	consumes Coefficient 1 in the selected biosynthetic direction.	4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP => 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP `RHEA:19894`	RHEA:19893 Source assertion: RHEA:19894 substrates contain CHEBI:30616 with coefficient 1. Source location `http://rdf.rhea-db.org/19894 rh:substrates; http://rdf.rhea-db.org/19893_L rh:contains1 http://rdf.rhea-db.org/Participant_19893_compound_6372; rh:compound http://rdf.rhea-db.org/Compound_6372`
4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP => 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP `RHEA:19894`	produces Coefficient 1 in the selected biosynthetic direction.	4-amino-2-methyl-5-diphosphonatooxymethylpyrimidine(3-) `CHEBI:57841`	RHEA:19893 Source assertion: RHEA:19894 products contain CHEBI:57841 with coefficient 1. Source location `http://rdf.rhea-db.org/19894 rh:products; http://rdf.rhea-db.org/19893_R rh:contains1 http://rdf.rhea-db.org/Participant_19893_compound_4541; rh:compound http://rdf.rhea-db.org/Compound_4541`
4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP => 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP `RHEA:19894`	produces Coefficient 1 in the selected biosynthetic direction.	ADP(3-) `CHEBI:456216`	RHEA:19893 Source assertion: RHEA:19894 products contain CHEBI:456216 with coefficient 1. Source location `http://rdf.rhea-db.org/19894 rh:products; http://rdf.rhea-db.org/19893_R rh:contains1 http://rdf.rhea-db.org/Participant_19893_compound_2710; rh:compound http://rdf.rhea-db.org/Compound_2710`
(R,Z)- 2-carboxylato-4-methyl-5-[(2-phosphonatooxy)ethylidene]-2,5-dihydrothiazole(3-) `CHEBI:62899`	consumes Coefficient 1 in the selected biosynthetic direction.	2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	RHEA:47844 Source assertion: RHEA:47845 substrates contain CHEBI:62899 with coefficient 1. Source location `http://rdf.rhea-db.org/47845 rh:substrates; http://rdf.rhea-db.org/47844_L rh:contains1 http://rdf.rhea-db.org/Participant_47844_compound_6833; rh:compound http://rdf.rhea-db.org/Compound_6833`
4-amino-2-methyl-5-diphosphonatooxymethylpyrimidine(3-) `CHEBI:57841`	consumes Coefficient 1 in the selected biosynthetic direction.	2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	RHEA:47844 Source assertion: RHEA:47845 substrates contain CHEBI:57841 with coefficient 1. Source location `http://rdf.rhea-db.org/47845 rh:substrates; http://rdf.rhea-db.org/47844_L rh:contains1 http://rdf.rhea-db.org/Participant_47844_compound_4541; rh:compound http://rdf.rhea-db.org/Compound_4541`
hydron `CHEBI:15378`	consumes Coefficient 2 in the selected biosynthetic direction.	2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	RHEA:47844 Source assertion: RHEA:47845 substrates contain CHEBI:15378 with coefficient 2. Source location `http://rdf.rhea-db.org/47845 rh:substrates; http://rdf.rhea-db.org/47844_L rh:contains2 http://rdf.rhea-db.org/Participant_47844_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	produces Coefficient 1 in the selected biosynthetic direction.	thiamine(1+) monophosphate(2-) `CHEBI:37575`	RHEA:47844 Source assertion: RHEA:47845 products contain CHEBI:37575 with coefficient 1. Source location `http://rdf.rhea-db.org/47845 rh:products; http://rdf.rhea-db.org/47844_R rh:contains1 http://rdf.rhea-db.org/Participant_47844_compound_5658; rh:compound http://rdf.rhea-db.org/Compound_5658`
2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	produces Coefficient 1 in the selected biosynthetic direction.	carbon dioxide `CHEBI:16526`	RHEA:47844 Source assertion: RHEA:47845 products contain CHEBI:16526 with coefficient 1. Source location `http://rdf.rhea-db.org/47845 rh:products; http://rdf.rhea-db.org/47844_R rh:contains1 http://rdf.rhea-db.org/Participant_47844_compound_4391; rh:compound http://rdf.rhea-db.org/Compound_4391`
2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	produces Coefficient 1 in the selected biosynthetic direction.	diphosphate(3-) `CHEBI:33019`	RHEA:47844 Source assertion: RHEA:47845 products contain CHEBI:33019 with coefficient 1. Source location `http://rdf.rhea-db.org/47845 rh:products; http://rdf.rhea-db.org/47844_R rh:contains1 http://rdf.rhea-db.org/Participant_47844_compound_2106; rh:compound http://rdf.rhea-db.org/Compound_2106`
thiamine(1+) monophosphate(2-) `CHEBI:37575`	consumes Coefficient 1 in the selected biosynthetic direction.	thiamine phosphate + ATP => thiamine diphosphate + ADP `RHEA:15914`	RHEA:15913 Source assertion: RHEA:15914 substrates contain CHEBI:37575 with coefficient 1. Source location `http://rdf.rhea-db.org/15914 rh:substrates; http://rdf.rhea-db.org/15913_L rh:contains1 http://rdf.rhea-db.org/Participant_15913_compound_5658; rh:compound http://rdf.rhea-db.org/Compound_5658`
ATP(4-) `CHEBI:30616`	consumes Coefficient 1 in the selected biosynthetic direction.	thiamine phosphate + ATP => thiamine diphosphate + ADP `RHEA:15914`	RHEA:15913 Source assertion: RHEA:15914 substrates contain CHEBI:30616 with coefficient 1. Source location `http://rdf.rhea-db.org/15914 rh:substrates; http://rdf.rhea-db.org/15913_L rh:contains1 http://rdf.rhea-db.org/Participant_15913_compound_6372; rh:compound http://rdf.rhea-db.org/Compound_6372`
thiamine phosphate + ATP => thiamine diphosphate + ADP `RHEA:15914`	produces Coefficient 1 in the selected biosynthetic direction.	thiamine(1+) diphosphate(3-) `CHEBI:58937`	RHEA:15913 Source assertion: RHEA:15914 products contain CHEBI:58937 with coefficient 1. Source location `http://rdf.rhea-db.org/15914 rh:products; http://rdf.rhea-db.org/15913_R rh:contains1 http://rdf.rhea-db.org/Participant_15913_compound_5328; rh:compound http://rdf.rhea-db.org/Compound_5328`
thiamine phosphate + ATP => thiamine diphosphate + ADP `RHEA:15914`	produces Coefficient 1 in the selected biosynthetic direction.	ADP(3-) `CHEBI:456216`	RHEA:15913 Source assertion: RHEA:15914 products contain CHEBI:456216 with coefficient 1. Source location `http://rdf.rhea-db.org/15914 rh:products; http://rdf.rhea-db.org/15913_R rh:contains1 http://rdf.rhea-db.org/Participant_15913_compound_2710; rh:compound http://rdf.rhea-db.org/Compound_2710`
L-cysteinyl-[cysteine desulfurase] + L-cysteine => S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + L-alanine `RHEA:17458`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6892 Source assertion: PWY-6892 lists RXN0-308; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6892"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:RXN0-308 Source assertion: RXN0-308 links to RHEA:17458. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:17457 Source assertion: RHEA:17457 has biosynthetically selected directional reaction RHEA:17458; the native cross-reference RHEA:17458 belongs to this family. Source location `http://rdf.rhea-db.org/17457 rh:directionalReaction and rh:bidirectionalReaction`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6892 Source assertion: PWY-6892 lists RXN-9789; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6892"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:RXN-9789 Source assertion: RXN-9789 links to RHEA:43345. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:43344 Source assertion: RHEA:43344 has biosynthetically selected directional reaction RHEA:43345; the native cross-reference RHEA:43345 belongs to this family. Source location `http://rdf.rhea-db.org/43344 rh:directionalReaction and rh:bidirectionalReaction`
D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6892 Source assertion: PWY-6892 lists DXS-RXN; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6892"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:DXS-RXN Source assertion: DXS-RXN links to RHEA:12606. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:12605 Source assertion: RHEA:12605 has biosynthetically selected directional reaction RHEA:12606; the native cross-reference RHEA:12606 belongs to this family. Source location `http://rdf.rhea-db.org/12605 rh:directionalReaction and rh:bidirectionalReaction`
L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6892 Source assertion: PWY-6892 lists RXN-11319; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6892"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:RXN-11319 Source assertion: RXN-11319 links to RHEA:26364. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:26361 Source assertion: RHEA:26361 has biosynthetically selected directional reaction RHEA:26362; the native cross-reference RHEA:26364 belongs to this family. Source location `http://rdf.rhea-db.org/26361 rh:directionalReaction and rh:bidirectionalReaction`
[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6892 Source assertion: PWY-6892 lists THIAZOLSYN2-RXN; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6892"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:THIAZOLSYN2-RXN Source assertion: THIAZOLSYN2-RXN links to RHEA:26300. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:26297 Source assertion: RHEA:26297 has biosynthetically selected directional reaction RHEA:26298; the native cross-reference RHEA:26300 belongs to this family. Source location `http://rdf.rhea-db.org/26297 rh:directionalReaction and rh:bidirectionalReaction`
5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6890 Source assertion: PWY-6890 lists PYRIMSYN1-RXN; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6890"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:PYRIMSYN1-RXN Source assertion: PYRIMSYN1-RXN links to RHEA:24841. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:24840 Source assertion: RHEA:24840 has biosynthetically selected directional reaction RHEA:24841; the native cross-reference RHEA:24841 belongs to this family. Source location `http://rdf.rhea-db.org/24840 rh:directionalReaction and rh:bidirectionalReaction`
4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP => 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP `RHEA:19894`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6890 Source assertion: PWY-6890 lists PYRIMSYN3-RXN; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6890"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:PYRIMSYN3-RXN Source assertion: PYRIMSYN3-RXN links to RHEA:19894. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:19893 Source assertion: RHEA:19893 has biosynthetically selected directional reaction RHEA:19894; the native cross-reference RHEA:19894 belongs to this family. Source location `http://rdf.rhea-db.org/19893 rh:directionalReaction and rh:bidirectionalReaction`
2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6894 Source assertion: PWY-6894 lists RXN-12611; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6894"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:RXN-12611 Source assertion: RXN-12611 links to RHEA:47845. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:47844 Source assertion: RHEA:47844 has biosynthetically selected directional reaction RHEA:47845; the native cross-reference RHEA:47845 belongs to this family. Source location `http://rdf.rhea-db.org/47844 rh:directionalReaction and rh:bidirectionalReaction`
thiamine phosphate + ATP => thiamine diphosphate + ADP `RHEA:15914`	part_of Native child-pathway membership is joined to the independently resolved current Rhea family; left-to-right is source orientation, not thermodynamic irreversibility.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6894 Source assertion: PWY-6894 lists THI-P-KIN-RXN; THISYN-PWY includes this child pathway. Source location `Pathway[@frameid="PWY-6894"]/reaction-list; super-pathways/Pathway[@frameid="THISYN-PWY"]` MetaCyc:THI-P-KIN-RXN Source assertion: THI-P-KIN-RXN links to RHEA:15914. Source location `Reaction/dblink[dblink-db='RHEA']/dblink-oid` RHEA:15913 Source assertion: RHEA:15913 has biosynthetically selected directional reaction RHEA:15914; the native cross-reference RHEA:15914 belongs to this family. Source location `http://rdf.rhea-db.org/15913 rh:directionalReaction and rh:bidirectionalReaction`
[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	part_of One current net sulfur-transfer reaction replaces the native two-step ThiI relay (RXN-14382 and RXN-9788). It retains IscS and ThiS carrier states but does not separately assert transient ThiI persulfide, ThiI/ThiF acyldisulfides, or specific ferredoxin chemistry.	`MetaCyc:THISYN-PWY`	MetaCyc:PWY-6892 Source assertion: PWY-6892 contains RXN-14382 and RXN-9788 for sulfur delivery from persulfidated cysteine desulfurase via ThiI to adenylated ThiS. Source location `Pathway/reaction-list; comment, About This Pathway` UniProtKB:P77718 Source assertion: ThiI is annotated with net RHEA:43340. Its attached PMID10753862 is a tRNA study and is not treated as direct evidence for ThiS chemistry. Source location `comments[commentType='CATALYTIC ACTIVITY']` RHEA:43340 Source assertion: RHEA:43341 is the left-to-right direction of net ThiS thiocarboxylation, including generic donor AH2 and acceptor A. Source location `http://rdf.rhea-db.org/43340 rh:directionalReaction; http://rdf.rhea-db.org/43341 rh:substrates and rh:products`
cysteine desulfurase `MetaCyc:CPLX0-248`	catalyzes IscS performs PLP-dependent cysteine desulfuration through its protein persulfide. The protein carrier class represents this catalytic state, not an additional freely diffusible metabolite.	L-cysteinyl-[cysteine desulfurase] + L-cysteine => S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + L-alanine `RHEA:17458`	MetaCyc:RXN0-308 Source assertion: ENZRXN0-251 assigns RXN0-308 to IscS complex CPLX0-248. Source location `Reaction/enzymatic-reaction/Enzymatic-Reaction[@frameid="ENZRXN0-251"]/enzyme` PMID:12860127 IscS is a widely distributed cysteine desulfurase that catalyzes the pyridoxal phosphate-dependent desulfuration of L-cysteine
Sulfur carrier protein ThiS adenylyltransferase `UniProtKB:P30138`	enables Functional ThiF enables ThiS adenylation; ThiF is homodimeric and ThiS-bound crystal assemblies contain two ThiF and two ThiS molecules. This gene-product edge does not assert monomer sufficiency.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H(+) => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphate `RHEA:43345`	UniProtKB:P30138 Source assertion: ThiF catalyzes RHEA:43344 adenylation of terminal Gly-Gly on ThiS; ECO:0000269, PMID9632726. Source location `comments[commentType='CATALYTIC ACTIVITY']` PMID:9632726 ThiF catalyzes the adenylation by ATP of the carboxyl-terminal glycine of ThiS. UniProtKB:P30138 Source assertion: ThiF is a homodimer; ECO:0000269, PMIDs15896804 and16388576. Source location `comments[commentType='SUBUNIT']` PMID:16388576 ThiS-ThiF is a heterotetramer consisting of a dimer of heterodimers.
tRNA sulfurtransferase `UniProtKB:P77718`	enables ThiI contributes to net sulfur transfer in the E. coli pathway. The primary reconstitution reports sevenfold stimulation, not isolated ThiI sufficiency or absolute requirement in every in vitro condition. The physiological reductant remains unspecified.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	UniProtKB:P77718 Source assertion: ThiI is annotated to transfer sulfur to ThiS, forming ThiS-thiocarboxylate, with sulfur donated as IscS persulfide. Source location `comments[commentType='FUNCTION']` PMID:10781607 ThiI, a known factor involved in both thiazole and s(4)U synthesis, stimulates this sulfur transfer step by 7-fold.
Cysteine desulfurase IscS `UniProtKB:P0A6B7`	enables IscS supplies sulfur for ThiS thiocarboxylation; the upstream desulfuration and this net transfer are distinct transformations. IscS/ThiF reconstitution can produce ThiS-COSH without ThiI under its assay conditions.	[ThiS sulfur-carrier protein]-C-terminal Gly-Gly-AMP + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] + AH2 => [ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + L-cysteinyl-[cysteine desulfurase] + A + AMP + 2 H(+) `RHEA:43341`	PMID:11438688 ThiS-COSH formation has been successfully reconstituted in vitro UniProtKB:P0A6B7 Source assertion: IscS delivers sulfur to partner proteins and transfers sulfur onto ThiI Cys-456; direct-study annotations include PMID10781607. Source location `comments[commentType='FUNCTION']`
Sulfur carrier protein ThiS `UniProtKB:O32583`	enables ThiS is the sulfur-carrier gene product. The three Rhea whole-protein state nodes distinguish its carboxylate, adenylate and thiocarboxylate forms; this role does not identify all state-class instances with one accession.	`MetaCyc:THISYN-PWY`	UniProtKB:O32583 Source assertion: ThiS is the sulfur donor for the thiazole phosphate moiety; ECO:0000269, PMID9632726. Source location `comments[commentType='FUNCTION']` UniProtKB:O32583 Source assertion: C-terminal thiocarboxylation proceeds via ThiF-dependent acyl adenylation and sulfur transfer; ECO:0000269, PMID9632726. Source location `comments[commentType='PTM']`
1-deoxy-D-xylulose-5-phosphate synthase `MetaCyc:CPLX0-743`	catalyzes Dxs supplies the DXP branch input and requires thiamine diphosphate itself; pathway connectivity does not imply cofactor-free initiation.	D-glyceraldehyde 3-phosphate + pyruvate + H(+) => 1-deoxy-D-xylulose 5-phosphate + CO2 `RHEA:12606`	MetaCyc:DXS-RXN Source assertion: ENZRXN0-1021 assigns DXS-RXN to CPLX0-743. Source location `Reaction/enzymatic-reaction/Enzymatic-Reaction[@frameid="ENZRXN0-1021"]/enzyme` UniProtKB:P77488 Source assertion: Dxs catalyzes RHEA:12605; the annotated physiological direction is RHEA:12606. ECO:0000269 catalytic evidence: PMIDs9371765 and9482846. Source location `comments[commentType='CATALYTIC ACTIVITY']`
thiazole synthase `MetaCyc:CPLX0-3949`	catalyzes ThiH within isolated ThiGH cleaves tyrosine using radical SAM chemistry. NADPH is the net reductant; primary assays used NADPH, flavodoxin 1 and flavoprotein:NADPH oxidoreductase under anaerobic conditions. These auxiliary assay proteins are not separately asserted pathway catalysts.	L-tyrosine + S-adenosyl-L-methionine + NADPH => 2-iminoacetate + 4-methylphenol + 5'-deoxyadenosine + L-methionine + NADP(+) `RHEA:26362`	UniProtKB:P30140 Source assertion: ThiH catalyzes RHEA:26361; ECO:0000269, PMIDs17403671 and17969213. Source location `comments[commentType='CATALYTIC ACTIVITY']` PMID:19923213 ThiH is a tyrosine lyase that cleaves the Cα–Cβ bond of tyrosine
thiazole synthase `MetaCyc:CPLX0-3949`	catalyzes ThiG performs the thiazole-forming reaction in the ThiGH system with ThiS thiocarboxylate. Exact tautomer stereochemistry follows current Rhea/UniProt; the 2009 product-structure experiment used B. subtilis and is not described as an E. coli-specific structural measurement.	[ThiS sulfur-carrier protein]-C-terminal-Gly-aminoethanethioate + 2-iminoacetate + 1-deoxy-D-xylulose 5-phosphate => [ThiS sulfur-carrier protein]-C-terminal Gly-Gly + 2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 2 H2O + H(+) `RHEA:26298`	UniProtKB:P30139 Source assertion: ThiG is annotated with RHEA:26297, consuming ThiS thiocarboxylate, dehydroglycine and DXP and producing the (2R,5Z) thiazole tautomer; this reaction comment has no attached ECO code. Source location `comments[commentType='CATALYTIC ACTIVITY']` PMID:17403671 The activity is shown to require four proteins isolated as heterodimers: ThiGH and ThiFS.
Phosphomethylpyrimidine synthase `UniProtKB:P30136`	enables ThiC supplies HMP-P. The E. coli protein annotation transfers the detailed radical-SAM chemistry from family evidence; direct E. coli cell-free reconstitution required an additional unidentified protein. Later purified structural and mechanistic studies used other bacterial ThiC proteins. Homodimer and cluster annotations are explicitly inferred.	5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-methionine => 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + CO + 5'-deoxyadenosine + formate + L-methionine + 3 H(+) `RHEA:24841`	UniProtKB:P30136 Source assertion: ThiC is assigned RHEA:24840 by ECO:0000255, HAMAP-Rule MF_00089. Source location `comments[commentType='CATALYTIC ACTIVITY']` PMID:15326535 The E. coli thiC gene product and an additional unidentified E. coli protein are required for the reaction. UniProtKB:P30136 Source assertion: ThiC is a homodimer by ECO:0000255, HAMAP-Rule MF_00089. Source location `comments[commentType='SUBUNIT']`
Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase `UniProtKB:P76422`	enables ThiD phosphorylates HMP-P. Current UniProt annotates a monomer from PMID10075431; the older native HMP-P-KIN-CPLX specifies a tetramer from a different study. The functional edge does not resolve that unresolved oligomer discrepancy. HMP salvage kinase activity is outside this de novo route.	4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + ATP => 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + ADP `RHEA:19894`	UniProtKB:P76422 Source assertion: ThiD catalyzes RHEA:19893 HMP-P phosphorylation; ECO:0000269, PMID10075431. Source location `comments[commentType='CATALYTIC ACTIVITY']` UniProtKB:P76422 Source assertion: ThiD is annotated as a monomer with ECO:0000269, PMID10075431. Source location `comments[commentType='SUBUNIT']` MetaCyc:HMP-P-KIN-CPLX Source assertion: The older native assembly contains four HMP-P-KIN-MONOMER subunits, citing Reddick et al. 1998; this differs from the current monomer annotation. Source location `Protein/component/coefficient; component/citation`
Thiamine-phosphate synthase `UniProtKB:P30137`	catalyzes ThiE couples the native nonaromatic carboxythiazole tautomer with HMP-PP, releasing CO2 and PPi. The structured annotation selects this substrate; detailed tautomer work on B. subtilis is supporting cross-species context, not proof of an identical measured E. coli substrate preference.	2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) => thiamine phosphate + CO2 + diphosphate `RHEA:47845`	UniProtKB:P30137 Source assertion: ThiE is annotated with RHEA:47844 for the (2R,5Z) tautomer. ECO:0000269 points to reference5, the 1995 Backstrom et al. JACS paper; the later tautomer-specific experiment is not that citation. Source location `comments[commentType='CATALYTIC ACTIVITY']` MetaCyc:RXN-12611 Source assertion: ENZRXN-19942 assigns the tautomer-dependent condensation RXN-12611 to THIE-MONOMER. Source location `Reaction/enzymatic-reaction/Enzymatic-Reaction[@frameid="ENZRXN-19942"]/enzyme`
Thiamine-monophosphate kinase `UniProtKB:P0AGG0`	catalyzes ThiL phosphorylates TMP to thiamine diphosphate. No metal-independent claim follows from the absence of a UniProt cofactor comment; neither thiamine salvage phosphorylation nor phosphatase routes are added.	thiamine phosphate + ATP => thiamine diphosphate + ADP `RHEA:15914`	UniProtKB:P0AGG0 Source assertion: ThiL catalyzes RHEA:15913; ECO:0000269, PMID4567662. Source location `comments[commentType='CATALYTIC ACTIVITY']` PMID:6284709 the latter lacks thiamine monophosphate kinase activity
Cysteine desulfurase IscS `UniProtKB:P0A6B7`	part_of Native stoichiometry: 2 subunits. The reviewed protein SUBUNIT annotation independently supports the homodimer.	cysteine desulfurase `MetaCyc:CPLX0-248`	MetaCyc:CPLX0-248 Source assertion: CPLX0-248 contains its mapped P0A6B7 gene product with native component coefficient 2. Source location `Protein/component/Protein and coefficient` UniProtKB:P0A6B7 Source assertion: Homodimer; supported by the reviewed direct-experiment SUBUNIT annotation. Source location `comments[commentType='SUBUNIT']` MetaCyc:G7325-MONOMER Source assertion: G7325-MONOMER has UniProt cross-reference P0A6B7. Source location `Protein/dblink[dblink-db='UNIPROT']/dblink-oid`
1-deoxy-D-xylulose-5-phosphate synthase `UniProtKB:P77488`	part_of Native stoichiometry: 2 subunits. The reviewed protein SUBUNIT annotation independently supports the homodimer.	1-deoxy-D-xylulose-5-phosphate synthase `MetaCyc:CPLX0-743`	MetaCyc:CPLX0-743 Source assertion: CPLX0-743 contains its mapped P77488 gene product with native component coefficient 2. Source location `Protein/component/Protein and coefficient` UniProtKB:P77488 Source assertion: Homodimer; supported by the reviewed direct-experiment SUBUNIT annotation. Source location `comments[commentType='SUBUNIT']` MetaCyc:DXS-MONOMER Source assertion: DXS-MONOMER has UniProt cross-reference P77488. Source location `Protein/dblink[dblink-db='UNIPROT']/dblink-oid`
Thiazole synthase `UniProtKB:P30139`	part_of Native stoichiometry: 6 subunits. The isolated complex comprises at least six ThiGH heterodimers in primary chromatography; this is not a universal cellular stoichiometry claim.	thiazole synthase `MetaCyc:CPLX0-3949`	MetaCyc:CPLX0-3949 Source assertion: CPLX0-3949 contains its mapped P30139 gene product with native component coefficient 6. Source location `Protein/component/Protein and coefficient` UniProtKB:P30139 Source assertion: Forms ThiGH heterodimers; ECO:0000269, PMID12650933. The native larger complex is an assembly of these heterodimeric units. Source location `comments[commentType='SUBUNIT']` PMID:19923213 at least six ThiGH heterodimers MetaCyc:THIG-MONOMER Source assertion: THIG-MONOMER has UniProt cross-reference P30139. Source location `Protein/dblink[dblink-db='UNIPROT']/dblink-oid`
2-iminoacetate synthase `UniProtKB:P30140`	part_of Native stoichiometry: 6 subunits. The isolated complex comprises at least six ThiGH heterodimers in primary chromatography; this is not a universal cellular stoichiometry claim.	thiazole synthase `MetaCyc:CPLX0-3949`	MetaCyc:CPLX0-3949 Source assertion: CPLX0-3949 contains its mapped P30140 gene product with native component coefficient 6. Source location `Protein/component/Protein and coefficient` UniProtKB:P30140 Source assertion: Forms ThiGH heterodimers; ECO:0000269, PMID12650933. The native larger complex is an assembly of these heterodimeric units. Source location `comments[commentType='SUBUNIT']` PMID:19923213 at least six ThiGH heterodimers MetaCyc:THIH-MONOMER Source assertion: THIH-MONOMER has UniProt cross-reference P30140. Source location `Protein/dblink[dblink-db='UNIPROT']/dblink-oid`
Cysteine desulfurase IscS `UniProtKB:P0A6B7`	has_cofactor PLP; direct-study support includes PMID12860127, with HAMAP evidence also present. The diprotic ChEBI form follows current UniProt.	pyridoxal 5'-phosphate(2-) `CHEBI:597326`	UniProtKB:P0A6B7 Source assertion: PLP; direct-study support includes PMID12860127, with HAMAP evidence also present. The diprotic ChEBI form follows current UniProt. Source location `comments[commentType='COFACTOR']`
Sulfur carrier protein ThiS adenylyltransferase `UniProtKB:P30138`	has_cofactor One Zn2+ per ThiF subunit; ECO:0000269, PMIDs15896804 and16388576. The primary structure places zinc away from the active site, consistent with a structural role.	zinc(2+) `CHEBI:29105`	UniProtKB:P30138 Source assertion: Binds one Zn2+ per ThiF subunit; ECO:0000269, PMIDs 15896804 and 16388576. Source location `comments[commentType='COFACTOR']` PMID:16388576 Source assertion: In the E. coli ThiF structure, zinc lies more than 20 Å from the active site; the authors interpret its role as most likely structural rather than catalytic. Source location `Results, ThiF active site, paragraph P21 (PMC2566941 section S11).`
2-iminoacetate synthase `UniProtKB:P30140`	has_cofactor One [4Fe-4S] cluster per ThiH subunit; ECO:0000269, PMIDs12650933 and17403671; three cysteine ligands plus exchangeable SAM.	tetra-mu3-sulfido-tetrairon `CHEBI:49883`	UniProtKB:P30140 Source assertion: One [4Fe-4S] cluster per ThiH subunit; ECO:0000269, PMIDs12650933 and17403671; three cysteine ligands plus exchangeable SAM. Source location `comments[commentType='COFACTOR']`
Phosphomethylpyrimidine synthase `UniProtKB:P30136`	has_cofactor One [4Fe-4S] cluster per ThiC subunit; ECO:0000255, HAMAP-Rule MF_00089. This is an inferred E. coli assignment, not an E. coli cluster-structure measurement.	tetra-mu3-sulfido-tetrairon `CHEBI:49883`	UniProtKB:P30136 Source assertion: One [4Fe-4S] cluster per ThiC subunit; ECO:0000255, HAMAP-Rule MF_00089. This is an inferred E. coli assignment, not an E. coli cluster-structure measurement. Source location `comments[commentType='COFACTOR']`
1-deoxy-D-xylulose-5-phosphate synthase `UniProtKB:P77488`	has_cofactor One Mg2+ per Dxs subunit; ECO:0000269, PMID17135236.	magnesium(2+) `CHEBI:18420`	UniProtKB:P77488 Source assertion: One Mg2+ per Dxs subunit; ECO:0000269, PMID17135236. Source location `comments[commentType='COFACTOR']`
1-deoxy-D-xylulose-5-phosphate synthase `UniProtKB:P77488`	has_cofactor Thiamine diphosphate is a bound Dxs cofactor; ECO:0000269, PMIDs9371765 and17135236.	thiamine(1+) diphosphate(3-) `CHEBI:58937`	UniProtKB:P77488 Source assertion: Thiamine diphosphate is a bound Dxs cofactor; ECO:0000269, PMIDs9371765 and17135236. Source location `comments[commentType='COFACTOR']`
Thiamine-phosphate synthase `UniProtKB:P30137`	has_cofactor ThiE binds Mg2+; ECO:0000250 by similarity, not a direct E. coli cofactor experiment.	magnesium(2+) `CHEBI:18420`	UniProtKB:P30137 Source assertion: ThiE binds Mg2+; ECO:0000250 by similarity, not a direct E. coli cofactor experiment. Source location `comments[commentType='COFACTOR']`

References

UniProtKB:P30136 Phosphomethylpyrimidine synthase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 175; actual body digest)
UniProtKB:P76422 Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 164; actual body digest)
UniProtKB:P30137 Thiamine-phosphate synthase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 187; actual body digest)
UniProtKB:P0AGG0 Thiamine-monophosphate kinase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 134; actual body digest)
UniProtKB:P30138 Sulfur carrier protein ThiS adenylyltransferase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 187; actual body digest)
UniProtKB:P30139 Thiazole synthase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 185; actual body digest)
UniProtKB:P30140 2-iminoacetate synthase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 174; actual body digest)
UniProtKB:P77718 tRNA sulfurtransferase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 180; actual body digest)
UniProtKB:P77488 1-deoxy-D-xylulose-5-phosphate synthase (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 199; actual body digest)
UniProtKB:P0A6B7 Cysteine desulfurase IscS (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 162; actual body digest)
UniProtKB:O32583 Sulfur carrier protein ThiS (source version: Reviewed full UniProt JSON retrieved 2026-10-11; entry version 161; actual body digest)
MetaCyc:THISYN-PWY superpathway of thiamine diphosphate biosynthesis I (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:PWY-6890 4-amino-2-methyl-5-diphosphomethylpyrimidine biosynthesis (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:PWY-6892 thiazole biosynthesis I (facultative anaerobic bacteria) (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:PWY-6894 thiamine diphosphate biosynthesis I (E. coli) (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:CPLX0-248 cysteine desulfurase (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:CPLX0-743 CPLX0-743 (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:CPLX0-3949 thiazole synthase (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
RHEA:17457 Rhea reaction family 17457 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:43344 Rhea reaction family 43344 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:43340 Rhea reaction family 43340 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:12605 Rhea reaction family 12605 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:26361 Rhea reaction family 26361 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:26297 Rhea reaction family 26297 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:24840 Rhea reaction family 24840 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:19893 Rhea reaction family 19893 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:47844 Rhea reaction family 47844 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
RHEA:15913 Rhea reaction family 15913 (source version: Rhea release 142, 2026-09-02; SHA-256 covers the complete compressed official RDF artifact)
MetaCyc:RXN0-308 RXN0-308 (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:RXN-9789 RXN-9789 (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:DXS-RXN DXS-RXN (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:RXN-11319 RXN-11319 (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:THIAZOLSYN2-RXN THIAZOLSYN2-RXN (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:PYRIMSYN1-RXN PYRIMSYN1-RXN (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:PYRIMSYN3-RXN PYRIMSYN3-RXN (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:RXN-12611 thiamin phosphate synthase (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:THI-P-KIN-RXN THI-P-KIN-RXN (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:RXN-14382 RXN-14382 (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:RXN-9788 RXN-9788 (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
PMID:12860127 Crystal structure of IscS, a cysteine desulfurase from Escherichia coli. (source version: Europe PMC indexed primary abstract and metadata retrieved 2026-10-11; not a full-text digest)
PMID:9632726 Thiamin biosynthesis in Escherichia coli. Identification of ThiS thiocarboxylate as the immediate sulfur donor in the thiazole formation. (source version: Europe PMC indexed primary abstract and metadata retrieved 2026-10-11; not a full-text digest)
PMID:10781607 The iscS gene in Escherichia coli is required for the biosynthesis of 4-thiouridine, thiamin, and NAD. (source version: Europe PMC indexed primary abstract and metadata retrieved 2026-10-11; not a full-text digest)
PMID:11438688 Biosynthesis of the thiazole moiety of thiamin in Escherichia coli: Identification of an acyldisulfide-linked protein–protein conjugate that is functionally analogous to the ubiquitin/E1 complex (source version: PMC full article HTML retrieved 2026-10-11; actual HTML digest)
PMID:19923213 Catalytic Activity of the Anaerobic Tyrosine Lyase Required for Thiamine Biosynthesis in Escherichia coli* (source version: PMC full article HTML retrieved 2026-10-11; actual HTML digest)
PMID:17403671 Thiazole synthase from Escherichia coli: an investigation of the substrates and purified proteins required for activity in vitro. (source version: Europe PMC indexed primary abstract and metadata retrieved 2026-10-11; not a full-text digest)
PMID:15326535 Biosynthesis of the thiamin pyrimidine: the reconstitution of a remarkable rearrangement reaction. (source version: Europe PMC indexed primary abstract and metadata retrieved 2026-10-11; not a full-text digest)
PMID:6284709 thiK and thiL loci of Escherichia coli. (source version: Europe PMC indexed primary abstract and metadata retrieved 2026-10-11; not a full-text digest)
PMID:16388576 Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis (source version: PMC full article HTML retrieved 2026-10-11; actual HTML digest)
MetaCyc:HMP-P-KIN-CPLX HMP-P-KIN-CPLX (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:G7325-MONOMER cysteine desulfurase (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:DXS-MONOMER 1-deoxy-D-xylulose-5-phosphate synthase (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:THIG-MONOMER 1-deoxy-D-xylulose 5-phosphate:thiol sulfurtransferase (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)
MetaCyc:THIH-MONOMER 2-iminoacetate synthase (source version: MetaCyc 22.5 native XML; retrieved 2026-10-11)

Curation history

2026-10-11T01:52:51Z Codex
- CREATE — Add the full thiamine diphosphate biosynthesis I superpathway.
  Curated exact MetaCyc:THISYN-PWY and all three native child branches. Ten current Rhea reactions represent eleven native steps because the ThiI net reaction subsumes two sulfur-transfer steps. Included whole carrier states, ThiGH assembly evidence, native source differences and exact precursor boundary. Source and duplicate-search dossiers are retained in research/pathway_additions/2026-10-11-next-pathways. Shared identifier authorities, generated pages, validation and independent reviews are recorded separately.
Read this curation session
2026-10-11T01:56:09Z Codex
- EDIT — Correct ThiF zinc evidence attribution after independent review.
  Issue 338: restricted UniProtKB:P30138 cofactor evidence to zinc binding and one ion per subunit; attached the structural-position and likely-role claim separately to PMID:16388576, Results / ThiF active site / P21. No nodes, reactions or pathway boundary changed. Independent reviewer verifies the corrected evidence against the retained primary source.
Read this curation session