Cysteine synthesis from O-phosphoserine

Reactome:R-MTU-936654

The CysM-CysO route in Mycobacterium tuberculosis transfers O-phosphoserine onto thiocarboxylated CysO, then Mec releases L-cysteine and regenerates the carrier. The graph begins at CysO-COSH: the upstream MoeZ sulfur-charging step is excluded because its physiological sulfur donor is unresolved. Carrier modification states, PLP-bearing CysM and the source zinc-containing, cleaved Mec assembly remain distinct.

Pathway type

biopax pathway

Organism scope

Mycobacterium tuberculosis NCBITaxon:1773

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Pathway network

15 nodes · 28 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.

Reaction / activity
Chemical / cofactor
Protein / complex
Cell / process context
Solid arrow: mechanistic relation
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
Mycobacterium tuberculosis `NCBITaxon:1773`	taxon
O-phosphonato-L-serine(2-) `CHEBI:57524`	small molecule
hydrogenphosphate `CHEBI:43474`	small molecule
water `CHEBI:15377`	small molecule
L-cysteine zwitterion `CHEBI:35235`	small molecule
zinc(2+) `CHEBI:29105`	cofactor
CysO `Reactome:R-MTU-936619`	protein
CysO-COSH `Reactome:R-MTU-936718`	protein
CysO-CO-Cys `Reactome:R-MTU-936690`	protein
PXLP-K51-CysM `Reactome:R-MTU-936710`	protein
Mec+ `Reactome:R-MTU-936660`	protein
CysM dimer `Reactome:R-MTU-936569`	complex
Mec-Zn++ `Reactome:R-MTU-936637`	complex
cytosol `GO:0005829`	cellular component
OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	molecular activity	left to right
cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	molecular activity	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
CysO-COSH `Reactome:R-MTU-936718`	consumes	OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction2 places physical entity Protein2 on its left side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction2/bp:left/#Protein2; #BiochemicalReaction2/bp:conversionDirection`
O-phosphonato-L-serine(2-) `CHEBI:57524`	consumes	OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction2 places physical entity SmallMolecule2 on its left side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction2/bp:left/#SmallMolecule2; #BiochemicalReaction2/bp:conversionDirection`
OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	produces	hydrogenphosphate `CHEBI:43474`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction2 places physical entity SmallMolecule3 on its right side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction2/bp:right/#SmallMolecule3; #BiochemicalReaction2/bp:conversionDirection`
OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	produces	CysO-CO-Cys `Reactome:R-MTU-936690`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction2 places physical entity Protein4 on its right side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction2/bp:right/#Protein4; #BiochemicalReaction2/bp:conversionDirection`
OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	occurs_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: All physical entities on both sides of BioPAX BiochemicalReaction2 have the same cellular location. Source location `#BiochemicalReaction2/bp:left\|bp:right; physicalEntity/bp:cellularLocation/#CellularLocationVocabulary1`
water `CHEBI:15377`	consumes	cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction3 places physical entity SmallMolecule4 on its left side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction3/bp:left/#SmallMolecule4; #BiochemicalReaction3/bp:conversionDirection`
CysO-CO-Cys `Reactome:R-MTU-936690`	consumes	cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction3 places physical entity Protein4 on its left side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction3/bp:left/#Protein4; #BiochemicalReaction3/bp:conversionDirection`
cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	produces	CysO `Reactome:R-MTU-936619`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction3 places physical entity Protein1 on its right side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction3/bp:right/#Protein1; #BiochemicalReaction3/bp:conversionDirection`
cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	produces	L-cysteine zwitterion `CHEBI:35235`	Reactome:R-MTU-936654 Source assertion: BioPAX BiochemicalReaction3 places physical entity SmallMolecule5 on its right side; conversion direction is LEFT-TO-RIGHT; displayed orientation is LEFT-TO-RIGHT. Source location `#BiochemicalReaction3/bp:right/#SmallMolecule5; #BiochemicalReaction3/bp:conversionDirection`
cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	occurs_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: All physical entities on both sides of BioPAX BiochemicalReaction3 have the same cellular location. Source location `#BiochemicalReaction3/bp:left\|bp:right; physicalEntity/bp:cellularLocation/#CellularLocationVocabulary1`
CysM dimer `Reactome:R-MTU-936569`	catalyzes	OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	Reactome:R-MTU-936654 Source assertion: BioPAX Catalysis2 names Complex1 as its catalytic controller. Source location `#Catalysis2/bp:controller/#Complex1; bp:controlled/#BiochemicalReaction2`
Mec-Zn++ `Reactome:R-MTU-936637`	catalyzes	cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	Reactome:R-MTU-936654 Source assertion: BioPAX Catalysis3 names Complex2 as its catalytic controller. Source location `#Catalysis3/bp:controller/#Complex2; bp:controlled/#BiochemicalReaction3`
L-cysteine zwitterion `CHEBI:35235`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity SmallMolecule5 is assigned to cellular location CellularLocationVocabulary1. Source location `#SmallMolecule5/bp:cellularLocation/#CellularLocationVocabulary1`
water `CHEBI:15377`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity SmallMolecule4 is assigned to cellular location CellularLocationVocabulary1. Source location `#SmallMolecule4/bp:cellularLocation/#CellularLocationVocabulary1`
hydrogenphosphate `CHEBI:43474`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity SmallMolecule3 is assigned to cellular location CellularLocationVocabulary1. Source location `#SmallMolecule3/bp:cellularLocation/#CellularLocationVocabulary1`
O-phosphonato-L-serine(2-) `CHEBI:57524`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity SmallMolecule2 is assigned to cellular location CellularLocationVocabulary1. Source location `#SmallMolecule2/bp:cellularLocation/#CellularLocationVocabulary1`
CysO-CO-Cys `Reactome:R-MTU-936690`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity Protein4 is assigned to cellular location CellularLocationVocabulary1. Source location `#Protein4/bp:cellularLocation/#CellularLocationVocabulary1`
CysO-COSH `Reactome:R-MTU-936718`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity Protein2 is assigned to cellular location CellularLocationVocabulary1. Source location `#Protein2/bp:cellularLocation/#CellularLocationVocabulary1`
CysO `Reactome:R-MTU-936619`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity Protein1 is assigned to cellular location CellularLocationVocabulary1. Source location `#Protein1/bp:cellularLocation/#CellularLocationVocabulary1`
Mec-Zn++ `Reactome:R-MTU-936637`	has_part	Mec+ `Reactome:R-MTU-936660`	Reactome:R-MTU-936654 Source assertion: BioPAX complex Complex2 explicitly includes physical entity Protein6. Source location `#Complex2/bp:component/#Protein6`
Mec-Zn++ `Reactome:R-MTU-936637`	has_part	zinc(2+) `CHEBI:29105`	Reactome:R-MTU-936654 Source assertion: BioPAX complex Complex2 explicitly includes physical entity SmallMolecule6. Source location `#Complex2/bp:component/#SmallMolecule6`
Mec-Zn++ `Reactome:R-MTU-936637`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity Complex2 is assigned to cellular location CellularLocationVocabulary1. Source location `#Complex2/bp:cellularLocation/#CellularLocationVocabulary1`
zinc(2+) `CHEBI:29105`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity SmallMolecule6 is assigned to cellular location CellularLocationVocabulary1. Source location `#SmallMolecule6/bp:cellularLocation/#CellularLocationVocabulary1`
Mec+ `Reactome:R-MTU-936660`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity Protein6 is assigned to cellular location CellularLocationVocabulary1. Source location `#Protein6/bp:cellularLocation/#CellularLocationVocabulary1`
CysM dimer `Reactome:R-MTU-936569`	has_part	PXLP-K51-CysM `Reactome:R-MTU-936710`	Reactome:R-MTU-936654 Source assertion: BioPAX complex Complex1 explicitly includes physical entity Protein5. Source location `#Complex1/bp:component/#Protein5`
CysM dimer `Reactome:R-MTU-936569`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity Complex1 is assigned to cellular location CellularLocationVocabulary1. Source location `#Complex1/bp:cellularLocation/#CellularLocationVocabulary1`
PXLP-K51-CysM `Reactome:R-MTU-936710`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-936654 Source assertion: BioPAX physical entity Protein5 is assigned to cellular location CellularLocationVocabulary1. Source location `#Protein5/bp:cellularLocation/#CellularLocationVocabulary1`
OPS is added to the carrier sulfide `Reactome:R-MTU-936665`	provides_input_for Source-ordered material transfer through Reactome:R-MTU-936690; no regulatory sign or stoichiometric coefficient is asserted.	cleavage of L-cysteine from carrier protein `Reactome:R-MTU-936747`	Reactome:R-MTU-936654 Source assertion: BioPAX PathwayStep2 explicitly lists PathwayStep3 as nextStep; the linked reactions produce and consume the same source physical entity. Source location `#PathwayStep2/bp:nextStep/#PathwayStep3; #BiochemicalReaction2/bp:right/#Protein4; #BiochemicalReaction2/bp:conversionDirection; #BiochemicalReaction3/bp:left/#Protein4; #BiochemicalReaction3/bp:conversionDirection`

References

PMID:16104727 Reconstitution of a new cysteine biosynthetic pathway in Mycobacterium tuberculosis
PMID:18842002 O-phospho-L-serine and the thiocarboxylated sulfur carrier protein CysO-COSH are substrates for CysM, a cysteine synthase from Mycobacterium tuberculosis
PMID:18799456 Cysteine synthase (CysM) of Mycobacterium tuberculosis is an O-phosphoserine sulfhydrylase: evidence for an alternative cysteine biosynthesis pathway in mycobacteria
Reactome:R-MTU-936654 BioPAX source pathway Reactome:R-MTU-936654 (source version: Reactome release 97)

Curation history

2026-10-07T07:37:21Z Codex
- CREATE — Curate Reactome:R-MTU-936654 with native physical states and reviewed chemistry
  Added 2 reactions and 28 edges from hash-pinned Reactome release 97. Complete source projection and edge-disposition ledger are in research/source_discovery/2026-10-07-reactome. Preserve modified, redox and cleaved protein states; exclude unsupported sulfur charging and CysK2/OAS chemistry where relevant; correct GTP coupling in sulfate activation. Exact source and primary-evidence limitations are explicit. Native and closed-schema validation passed before writing. Hidden/ignored-file deduplication included.
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