Bacterial L-cysteine biosynthesis via O-acetyl-L-serine

A reusable two-step bacterial pathway in which serine O-acetyltransferase converts L-serine and acetyl-CoA to O-acetyl-L-serine, followed by a pyridoxal-phosphate-dependent O-acetylserine sulfhydrylase that incorporates sulfide to produce L-cysteine. The terminal reaction may be implemented by a CysK-type or CysM-type enzyme. Sulfide generation by assimilatory sulfate reduction or other sulfur-acquisition pathways supplies an input but is not part of this module.

MODULE:bacterial_cysteine_biosynthesis_via_o_acetylserineDRAFTMetabolic Pathwaymodules/bacterial_cysteine_biosynthesis_via_o_acetylserine.yaml
cysteine biosynthesis from serineGO:0019344
GO:0019344
L-cysteine biosynthetic process
GO:0019344 grounds the module. The route-specific term GO:0006535 (L-cysteine biosynthetic process from L-serine) was obsoleted in GO release 2026-07-26 with replaced_by GO:0019344; the O-acetylserine route is carried by the module structure rather than by the term.
PMID:10482527
Pathways of assimilative sulfur metabolism in Pseudomonas putida
Pseudomonas putida S-313 cell extracts showed substantial O-acetylserine sulfhydrylase activity, providing organism-level evidence that this terminal chemistry operates in P. putida.
PMID:42278617
Serine Acetyltransferase from Pseudomonas aeruginosa: Distinctive Features, Pleiotropic Roles, and Therapeutic Potential.
Biochemical and deletion analysis identifies PA3816/Q9HXI6 as the major Pseudomonas aeruginosa serine acetyltransferase, grounding the first reaction in a closely related Pseudomonas species.
PMID:41541697
De novo cysteine biosynthesis in Pseudomonas aeruginosa: Characterization of the two main cysteine synthase isoforms.
Biochemical and genetic analysis establishes CysK and CysM as partially redundant O-acetylserine sulfhydrylases with distinct sulfur-donor preferences in Pseudomonas aeruginosa.
PMID:41676964
Distinct contributions of O-acetylserine sulfhydrylases to cysteine biosynthesis in Pseudomonas aeruginosa
Direct biochemical and genetic work in Pseudomonas aeruginosa supports partially redundant CysK/CysM pathway roles, CysM thiosulfate preference, and absence of detectable binding between CysK and endogenous CysE1.
file:PSEPK/cysE/cysE-ai-review.yaml
PSEPK CysE gene review
The exact Q88PL0 record and curated review ground serine O-acetylation in the KT2440 instance.
file:PSEPK/cysK/cysK-ai-review.yaml
PSEPK CysK gene review
The exact Q88E95 record and curated review ground the CysK sulfide route in the KT2440 instance.
file:PSEPK/cysM/cysM-ai-review.yaml
PSEPK CysM gene review
The exact Q88MC0 record and curated review ground a CysM-family alternative for the same sulfide-dependent reaction in KT2440.
5Nodes
2Parts
1Variant Sets
2Variants
3Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bacterial_cysteine_biosynthesis_via_o_acetylserine deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • serine_o_acetylation → sulfide_incorporation [NOT_CHECKED]
    O-acetyl-L-serine produced by serine O-acetyltransferase is the substrate consumed by either terminal sulfhydrylase variant.

Gene-review completeness (3/8 grounded genes reviewed)

3 complete review(s) · 1 with deep research · 5 missing review · 2 reviewed but lacking deep research

Gene Review Complete Deep research
cysE Q88PL0 ✓ ✓ ✗
cysK Q88E95 ✓ ✓ ✓
cysM Q88MC0 ✓ ✓ ✗
CysE (Escherichia coli K-12) P0A9D4 ✗ — —
CysK (Escherichia coli K-12) P0ABK5 ✗ — —
CysM (Escherichia coli K-12) P16703 ✗ — —
CysE (Pseudomonas aeruginosa PAO1) Q9HXI6 ✗ — —
CysM (Pseudomonas aeruginosa PAO1) Q9I526 ✗ — —

Details

Bacterial L-cysteine biosynthesis via O-acetyl-L-serineMetabolic Pathwaybacterial_cysteine_biosynthesis_via_o_acetylserine
cysteine biosynthesis from serineGO:0019344

Sulfate transport, sulfate activation, APS/PAPS reduction, and sulfite reduction are upstream sulfur-assimilation context, not module parts. The CysK and CysM alternatives are modeled separately because their family assignments and possible substrate ranges differ even though both current PSEPK records carry GO:0004124.

Connections

Part 1: serine O-acetylation
Formation of O-acetyl-L-serineReactionserine_o_acetylation

Annotons

Serine O-acetyltransferase activity
cysE_activity
Participant: Family: Serine acetyltransferase family
Family:
Serine acetyltransferase familyInterPro:IPR005881
Representative Members: CysE (Pseudomonas putida KT2440)UniProtKB:Q88PL0 CysE (Escherichia coli K-12)UniProtKB:P0A9D4 CysE (Pseudomonas aeruginosa PAO1)UniProtKB:Q9HXI6

Function

L-serine O-acetyltransferase activityGO:0009001
Substrates: L-serineCHEBI:33384 acetyl-CoACHEBI:57288
Products: O-acetyl-L-serineCHEBI:58340 coenzyme ACHEBI:57287

Transfers an acetyl group from acetyl-CoA to L-serine to form O-acetyl-L-serine, the carbon skeleton consumed by the terminal sulfhydrylation step.

Part 2: sulfide incorporation
Formation of L-cysteine from O-acetyl-L-serine and sulfideReactionsulfide_incorporation
Variant set: O-acetylserine sulfhydrylase variant by enzyme family variant (One Or More)
CysK-type O-acetylserine sulfhydrylaseReactioncysK_variant

Annotons

CysK-type cysteine synthase activity
cysK_activity
Participant: Family: CysK-type O-acetylserine sulfhydrylase family
Family:
CysK-type O-acetylserine sulfhydrylase familyInterPro:IPR005859
Representative Members: CysK (Pseudomonas putida KT2440)UniProtKB:Q88E95 CysK (Escherichia coli K-12)UniProtKB:P0ABK5

Function

cysteine synthase activityGO:0004124
Substrates: O-acetyl-L-serineCHEBI:58340 hydrosulfideCHEBI:29919
Products: L-cysteineCHEBI:35235 acetateCHEBI:30089
Cofactors: pyridoxal 5'-phosphateCHEBI:597326

PLP-dependent incorporation of sulfide into O-acetyl-L-serine to produce L-cysteine.

CysM-type O-acetylserine sulfhydrylaseReactioncysM_variant

Annotons

CysM-type cysteine synthase activity
cysM_activity
Participant: Family: CysM-type O-acetylserine sulfhydrylase family
Family:
CysM-type O-acetylserine sulfhydrylase familyInterPro:IPR005858
Representative Members: CysM (Pseudomonas putida KT2440)UniProtKB:Q88MC0 CysM (Escherichia coli K-12)UniProtKB:P16703 CysM (Pseudomonas aeruginosa PAO1)UniProtKB:Q9I526

Function

cysteine synthase activityGO:0004124
Substrates: O-acetyl-L-serineCHEBI:58340 hydrosulfideCHEBI:29919
Products: L-cysteineCHEBI:35235 acetateCHEBI:30089
Cofactors: pyridoxal 5'-phosphateCHEBI:597326

Alternative PLP-dependent O-acetylserine sulfhydrylase implementation; physiological substrate breadth can differ among CysM-family proteins and must be assessed per taxon.