cds1

UniProt ID: Q9KT44
Organism: Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Review Status: IN PROGRESS
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Gene Description

L-cysteine desulfhydrase (Cds1) is the principal enzyme for cysteine-derived hydrogen sulfide (H2S) production in V. cholerae. It catalyzes the PLP-dependent conversion of L-cysteine to hydrogen sulfide, pyruvate, and ammonia (EC 4.4.1.1). The enzyme-derived H2S protects V. cholerae from oxidative stress by enhancing catalase activity and promoting iron storage, thereby facilitating host colonization. Note that in organism-specific literature, this gene is referred to as cbs (cystathionine beta-synthase), though the demonstrated functional activity is L-cysteine desulfhydrase.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0019344 L-cysteine biosynthetic process
IBA
GO_REF:0000033
REMOVE
Summary: This annotation represents a cysteine biosynthetic function, but experimental evidence from Ma et al. (2021) demonstrates that VC1061/cds1 functions primarily in cysteine catabolism to produce H2S, not biosynthesis. The IBA annotation is based on phylogenetic inference from orthologs that may include cysteine synthases, but the V. cholerae enzyme has been experimentally characterized as a cysteine desulfhydrase that degrades cysteine.
Reason: The annotation is incorrect for this specific gene. Ma et al. (2021) clearly demonstrate that VC1061 is the principal enzyme for H2S production FROM cysteine degradation, not cysteine biosynthesis. Deletion of VC1061 drastically reduces H2S production from cysteine, indicating a catabolic rather than biosynthetic role. The phylogenetic inference from IBA incorrectly propagated function from related cysteine synthases (SF194/SF162) that catalyze the reverse reaction. MSA analysis of PTHR10314 family reveals: (1) SF135 (Cds1/desulfhydrases) has a distinct active site signature motif (ASSGST) vs synthases (PTSGNTG); (2) SF135 shares only ~24% sequence identity with synthases, less than synthases share with each other (43%); (3) SF135 has the longest branch length (0.528) from the family root, indicating greatest divergence and neo-functionalization; (4) different EC class - 4.4.1.1 (lyase/catabolism) vs 2.5.1.47 (transferase/biosynthesis). The source proteins in the IBA WITH/FROM field (P0ABK5/CysK, P35520/CBS, P16703/CysM) are from SF194/SF162 synthase subfamilies, but Q9KT44/VC1061 is in SF135 which evolved a catabolic function.
Supporting Evidence:
PMID:34283874
The results indicate that deletion of cbs is critical in reducing H2S production from cysteine in V. cholerae
file:VIBCH/cds1/cds1-deep-research-falcon.md
Among the mutants of CBS candidates, only Δvc1061 showed a significant reduction in H2S production from cysteine
file:interpro/panther/PTHR10314/PTHR10314-notes.md
SF135 (Cds1) has a distinct active site signature motif (ASSGST) vs synthases (PTSGNTG); SF135 shares only ~24% identity with synthases; longest branch length (0.528) indicates neo-functionalization
GO:0005737 cytoplasm
IBA
GO_REF:0000033
ACCEPT
Summary: Cytoplasmic localization is consistent with the function of this PLP-dependent enzyme. UniProt annotation (HAMAP-Rule:MF_00868) also indicates cytoplasmic localization, supported by both homology inference and computational prediction.
Reason: Cytoplasmic localization is well-supported by both phylogenetic inference (IBA) and computational methods. PLP-dependent enzymes of this class are typically cytoplasmic, and there is no evidence for any alternative localization. This represents a core aspect of the protein's function.
Supporting Evidence:
file:VIBCH/cds1/cds1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0004124 cysteine synthase activity
IEA
GO_REF:0000003
MODIFY
Summary: This annotation is based on EC:2.5.1.47 mapping, which assigns cysteine synthase activity (O-acetyl-L-serine + H2S -> L-cysteine + acetate). However, the primary experimentally demonstrated activity for VC1061 is the opposite reaction - L-cysteine desulfhydrase activity (EC 4.4.1.1), which degrades cysteine to produce H2S.
Reason: The EC mapping to cysteine synthase (EC 2.5.1.47) is incorrect for this enzyme. Ma et al. (2021) demonstrated that VC1061 is the principal H2S-producing enzyme from cysteine degradation in V. cholerae. UniProt correctly annotates this enzyme with EC 4.4.1.1 (L-cysteine desulfhydrase) via HAMAP-Rule:MF_00868. The correct molecular function term is GO:0080146 (L-cysteine desulfhydrase activity).
Supporting Evidence:
PMID:34283874
degradation of L-cysteine is the main source of H2S production in V. cholerae and the ortholog of CBS is the critical enzyme involved in the related biochemical reaction
GO:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: Duplicate cytoplasm annotation from combined automated methods. This is consistent with the IBA annotation and represents a valid localization for this enzyme.
Reason: This annotation is redundant with the IBA annotation for cytoplasm but remains valid. Multiple lines of computational evidence (UniRule, HAMAP, ARBA) support cytoplasmic localization for Cds1-family enzymes.
Supporting Evidence:
file:VIBCH/cds1/cds1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0016829 lyase activity
IEA
GO_REF:0000043
ACCEPT
Summary: Lyase activity is a high-level term that correctly captures the general enzymatic class of L-cysteine desulfhydrases. The enzyme catalyzes a carbon-sulfur lyase reaction (C-S bond cleavage), which is classified under lyases (EC 4.x.x.x).
Reason: While this is a broad term, it is not incorrect. L-cysteine desulfhydrase (EC 4.4.1.1) is indeed a lyase that cleaves C-S bonds. This annotation provides useful high-level classification, though more specific terms (GO:0080146) should also be present. Keeping this annotation maintains appropriate ontology hierarchy representation.
Supporting Evidence:
file:VIBCH/cds1/cds1-uniprot.txt
Lyase
GO:0019450 obsolete L-cysteine catabolic process to pyruvate
IEA
GO_REF:0000120
ACCEPT
Summary: This biological process annotation correctly captures the catabolic role of Cds1. The enzyme converts L-cysteine to pyruvate (plus H2S and ammonia), which is precisely the process described by this GO term.
Reason: This annotation accurately represents the core biological process in which Cds1 participates. Ma et al. (2021) demonstrated that VC1061 is the principal enzyme for cysteine-derived H2S production, and the canonical desulfhydrase reaction yields pyruvate as a product. This annotation derived from InterPro:IPR047586 (Cds1 family) is correct and represents a core function of the gene.
Supporting Evidence:
PMID:34283874
degradation of L-cysteine is the main source of H2S production in V. cholerae
GO:0030170 pyridoxal phosphate binding
IEA
GO_REF:0000104
ACCEPT
Summary: PLP binding is essential for Cds1 catalytic activity. The enzyme belongs to the TrpB-like PLP-dependent superfamily, and UniProt annotation indicates the PLP binding site at Lys54 (N6-(pyridoxal phosphate)lysine modification).
Reason: This annotation is well-supported by sequence features and domain architecture. The protein contains a TrpB-like PALP fold (IPR001926, PF00291) and has a defined PLP binding site at Lys54. PLP is the required cofactor for cysteine desulfhydrase activity, making this annotation essential for understanding the enzyme's mechanism.
Supporting Evidence:
file:VIBCH/cds1/cds1-uniprot.txt
N6-(pyridoxal phosphate)lysine
GO:1901605 alpha-amino acid metabolic process
IEA
GO_REF:0000117
ACCEPT
Summary: This is a high-level biological process term indicating involvement in amino acid metabolism. While correct, it is very general compared to the more specific GO:0019450 (L-cysteine catabolic process to pyruvate) that is also annotated.
Reason: This annotation is correct but provides less specific information than GO:0019450. It is acceptable to retain as it provides ontological context and is not incorrect. The ARBA machine learning model correctly identified the metabolic role of this enzyme.
Supporting Evidence:
file:VIBCH/cds1/cds1-uniprot.txt
L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+)
GO:0080146 L-cysteine desulfhydrase activity
IDA
PMID:34283874
CBS-derived H2S facilitates host colonization of Vibrio chol...
NEW
Summary: This is the correct molecular function term for Cds1 based on experimental evidence. Ma et al. (2021) demonstrated that VC1061 is the principal enzyme for H2S production from L-cysteine in V. cholerae. The reaction is: L-cysteine + H2O = ammonia + pyruvate + hydrogen sulfide + H+.
Reason: This annotation should be added as the primary molecular function for Cds1. The existing GO:0004124 (cysteine synthase activity) annotation is incorrect for this enzyme. Genetic deletion experiments clearly demonstrate that VC1061 is the key enzyme for cysteine-to-H2S conversion. This term (GO:0080146) precisely matches EC 4.4.1.1 assigned by HAMAP.
Supporting Evidence:
PMID:34283874
CBS is the key enzyme for H2S production in V. cholerae
GO:0070814 hydrogen sulfide biosynthetic process
IDA
PMID:34283874
CBS-derived H2S facilitates host colonization of Vibrio chol...
NEW
Summary: Cds1 is the principal enzyme responsible for hydrogen sulfide (H2S) biosynthesis in V. cholerae through cysteine degradation. Ma et al. (2021) demonstrated that deletion of VC1061 drastically reduces H2S production from cysteine.
Reason: This biological process annotation should be added to reflect the primary physiological role of Cds1 in V. cholerae. The enzyme-derived H2S has important downstream effects including oxidative stress resistance and enhanced catalase activity. This term captures the biosynthetic aspect of H2S production that is central to the enzyme's function.
Supporting Evidence:
PMID:34283874
degradation of cysteine is the largest contributor of H2S in V. cholerae
GO:0034599 cellular response to oxidative stress
IMP
PMID:34283874
CBS-derived H2S facilitates host colonization of Vibrio chol...
NEW
Summary: The H2S produced by Cds1 protects V. cholerae from oxidative stress by enhancing catalase (KatB) activity. Deletion mutants show approximately 10-fold lower viability under H2O2 stress compared to wild-type.
Reason: Experimental evidence from Ma et al. (2021) demonstrates that Cds1-derived H2S is essential for oxidative stress resistance. The phenotype (reduced survival under H2O2) of cbs/VC1061 deletion mutants supports IMP evidence for involvement in this process. However, this may be considered a downstream effect rather than a core function of the enzyme, so could alternatively be marked as KEEP_AS_NON_CORE.
Supporting Evidence:
PMID:34283874
deletion of cbs led to a 10-fold reduction in viability compared to the wild-type under intense H2O2 stress

Core Functions

Catalyzes PLP-dependent beta-elimination of L-cysteine to produce hydrogen sulfide, pyruvate, and ammonia; principal source of endogenous H2S in V. cholerae

Supporting Evidence:
  • PMID:34283874
    degradation of L-cysteine is the main source of H2S production in V. cholerae and the ortholog of CBS is the critical enzyme involved
  • file:VIBCH/cds1/cds1-uniprot.txt
    L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+)

References

Gene Ontology annotation based on Enzyme Commission mapping
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
CBS-derived H2S facilitates host colonization of Vibrio cholerae by promoting the iron-dependent catalase activity of KatB
  • VC1061 is the principal enzyme for cysteine-derived H2S production in V. cholerae
    "The results indicate that deletion of cbs is critical in reducing H2S production from cysteine in V. cholerae"
  • CBS-derived H2S protects V. cholerae from oxidative stress
    "deletion of cbs led to a 10-fold reduction in viability compared to the wild-type under intense H2O2 stress"
  • H2S enhances catalase activity at post-translational level
    "CBS-derived H2S enhances catalase activity in V. cholerae"
  • CBS-derived H2S facilitates host colonization under high ROS conditions
    "In the high ROS model, the cbs mutant (Δcbs) was outcompeted by wild-type (WT)"
file:VIBCH/cds1/cds1-deep-research-falcon.md
Deep research summary for cds1 (VC1061) in Vibrio cholerae
  • VC1061 is the principal enzyme for cysteine-derived H2S production
    "Among the mutants of CBS candidates, only Δvc1061 showed a significant reduction in H2S production from cysteine"
  • CBS is the key enzyme for H2S production in V. cholerae
    "CBS is the key enzyme for H2S production in V. cholerae"
  • CBS-derived H2S protects V. cholerae from oxidative stress via catalase activation
    "Endogenous H2S driven by cbs/VC1061 protects V. cholerae from H2O2"
  • Cysteine desulfhydrase reaction produces H2S, pyruvate, and ammonia
    "The canonical cysteine desulfhydrase reaction yields H2S + pyruvate + NH3 from L-cysteine"
file:VIBCH/cds1/cds1-uniprot.txt
UniProt entry for Q9KT44 (Cds1, Vibrio cholerae)
  • Protein is localized to cytoplasm
    "SUBCELLULAR LOCATION: Cytoplasm"
  • Enzyme is a PLP-dependent lyase
    "Lyase"
  • PLP binding site at Lys54
    "N6-(pyridoxal phosphate)lysine"
  • Catalytic reaction produces H2S, pyruvate, and ammonia
    "L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+)"

Deep Research

Falcon

(cds1-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 13 citations 2026-01-05T22:17:25.945313

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan
- Verify gene/protein identity and resolve symbol ambiguity for VC_1061 in Vibrio cholerae O1 El Tor N16961 (N16961). Use organism- and locus-specific primary literature to anchor identity. (Completed using Ma et al., 2021.) (ma2021cbsderivedh2sfacilitates pages 2-4, ma2021cbsderivedh2sfacilitates pages 4-6)
- Gather recent, authoritative sources on V. cholerae cysteine-derived H2S production and PLP-dependent enzymes; prioritize 2023–2024 for broader bacterial H2S context. (Completed using Shahid & Bhatia, 2024; Nguyen‑tiet et al., 2024.) (shahid2024hydrogensulfidea pages 1-3, shahid2024hydrogensulfidea pages 3-4, nguyentiet2024identificationofbacteria pages 7-10, nguyentiet2024identificationofbacteria pages 16-19)
- Extract mechanistic, pathway, and phenotypic evidence (oxidative stress resistance, catalase activation, iron handling; in vivo colonization). (Completed using Ma et al., 2021.) (ma2021cbsderivedh2sfacilitates pages 4-6, ma2021cbsderivedh2sfacilitates pages 21-22, ma2021cbsderivedh2sfacilitates pages 2-4, ma2021cbsderivedh2sfacilitates pages 13-15)
- Synthesize a comprehensive, well‑cited report with URLs and publication dates; highlight applications and expert perspectives. (This report.)

Comprehensive research report: cds1 (VC_1061) / UniProt Q9KT44 in Vibrio cholerae O1 El Tor N16961

Gene/protein identity and symbol disambiguation
- Organism and locus: The target is Vibrio cholerae O1 El Tor N16961, locus tag VC_1061. Primary literature on V. cholerae explicitly manipulates and complements VC1061 and refers to it functionally as cbs (cystathionine β‑synthase), with “CBS‑derived H2S” as the conceptual designation. For example: “Among the mutants of CBS candidates, only Δvc1061 showed a significant reduction in H2S production from cysteine,” and chromosomal complementation is described as “cbs (VC1061).” PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 4-6, ma2021cbsderivedh2sfacilitates pages 13-15, ma2021cbsderivedh2sfacilitates pages 2-4)
- Symbol ambiguity: The user’s UniProt record (Q9KT44) names the gene cds1 and annotates an L‑cysteine desulfhydrase–like PLP enzyme. In contrast, organism‑specific literature for VC1061 uses cbs and places the protein in the CBS/CSE/3MST cysteine‑degradation context. Given this discrepancy, the most reliable anchor is the locus tag (VC1061) in V. cholerae N16961; experimental evidence ties VC1061 to cysteine‑derived H2S and oxidative stress phenotypes under the gene name cbs in that work (see below). (ma2021cbsderivedh2sfacilitates pages 2-4, ma2021cbsderivedh2sfacilitates pages 4-6)

Key concepts and definitions (current understanding)
- Cysteine‑derived bacterial H2S: Bacteria produce H2S via several routes. Beyond classical sulfate reducers, many bacteria generate H2S by degrading L‑cysteine. A 2024 review summarizes three major contributors: (1) dissimilatory sulfate‑reducing bacteria; (2) sulfite reductase pathways in diverse bacteria; and (3) cysteine‑degrading enzymes (cysteine desulfhydrases and related PLP enzymes) that convert L‑cysteine to H2S, ammonia, and pyruvate. Biomolecules, Sept 2024; https://doi.org/10.3390/biom14091145 (shahid2024hydrogensulfidea pages 1-3, shahid2024hydrogensulfidea pages 3-4)
- In V. cholerae, cysteine degradation is the dominant H2S source: Genetic analysis showed that deletion of cbs (VC1061) drastically reduces H2S from L‑cysteine, while deletions targeting assimilatory sulfite reduction (cysI/cysJ) had little effect on H2S output under the tested conditions. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 4-6)
- Mechanistic reaction (cysteine desulfhydrase‑type chemistry): The canonical cysteine desulfhydrase reaction yields H2S + pyruvate + NH3 from L‑cysteine; this is the concise definition employed in recent reviews for bacterial cysteine desulfhydrase activity, framing the chemistry relevant to VC1061’s phenotype in V. cholerae. Biomolecules, Sept 2024; https://doi.org/10.3390/biom14091145 (shahid2024hydrogensulfidea pages 1-3, shahid2024hydrogensulfidea pages 3-4)

Primary function, substrates, products, and cofactor
- Experimental role of VC1061 in V. cholerae: Ma et al. designate VC1061 as a CBS candidate and demonstrate that Δvc1061 uniquely reduces H2S production from cysteine among CBS‑candidate mutants; they further refer to “CBS‑derived H2S” throughout. Their approach does not provide purified‑enzyme kinetics, but the cellular phenotypes (H2S readouts, stress resistance, complementation) establish that the VC1061 gene product is the principal contributor to cysteine‑derived H2S in their system. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 2-4, ma2021cbsderivedh2sfacilitates pages 4-6)
- Reaction context: While literature names VC1061 “CBS,” the dominant functional outcome is H2S generation from L‑cysteine in vivo. This outcome is consistent with PLP‑dependent β‑elimination chemistry typical of cysteine desulfhydrases (H2S + pyruvate + NH3). (Definition from 2024 review). Biomolecules, Sept 2024; https://doi.org/10.3390/biom14091145 (shahid2024hydrogensulfidea pages 1-3, shahid2024hydrogensulfidea pages 3-4)

Biological processes, pathway context, and localization
- Oxidative stress resistance via catalase activation and iron handling: Endogenous H2S driven by cbs/VC1061 protects V. cholerae from H2O2. Δcbs shows ~10‑fold lower viability under intense H2O2; complementation rescues survival. H2S scavenging with heterologous SQR partly abolishes protection, demonstrating H2S as the effector. CBS‑derived H2S enhances catalase activity (especially KatB) predominantly at a post‑translational level, associated with higher iron content in catalase and increased iron storage (Dps). PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 4-6, ma2021cbsderivedh2sfacilitates pages 6-7, ma2021cbsderivedh2sfacilitates pages 7-10, ma2021cbsderivedh2sfacilitates pages 10-11)
- Host colonization: In adult mouse models, a cbs mutant is outcompeted by WT under high‑ROS conditions; complementation restores fitness, indicating CBS‑dependent H2S facilitates host colonization through oxidative stress mitigation. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 10-11)
- Broader Vibrionaceae cysteine‑to‑H2S metabolism: Environmental metagenomic/metatranscriptomic work in 2024 bioRxiv reactors links Vibrionaceae (including Vibrio MAGs) with cyuA‑encoded cysteine desulfidase/desulfhydrase pathways and shows that cysteine enrichment rapidly induces H2S, ammonium, acetate and upregulates cyuA versus sulfate conditions—supporting the prevalence and rapidity of cysteine‑derived H2S in Vibrionaceae guilds. bioRxiv, Aug 2024; https://doi.org/10.1101/2024.04.12.589155 (nguyentiet2024identificationofbacteria pages 7-10, nguyentiet2024identificationofbacteria pages 13-16, nguyentiet2024identificationofbacteria pages 16-19)

Recent developments and latest research (2023–2024 emphasis)
- 2024 review: Consolidates microbial H2S biogenesis routes and frames cysteine desulfhydrases as key bacterial sources, with the canonical reaction definition (cysteine → H2S + pyruvate + NH3). This provides current consensus terminology aligning with the user’s UniProt annotation (desulfhydrase activity) and the V. cholerae phenotype reported in 2021. Biomolecules, Sept 2024; https://doi.org/10.3390/biom14091145 (shahid2024hydrogensulfidea pages 1-3, shahid2024hydrogensulfidea pages 3-4)
- 2024 environmental study: Demonstrates that in mixed communities seeded from aquaculture systems, cysteine enrichment selects for Vibrionaceae and strongly upregulates cyuA; H2S appears faster from cysteine than from sulfate (51–82 mg H2S/L by day 5 versus 14–28 days to reach similar levels under sulfate; short incubations: ≈10 ± 7.9 mg H2S/L/d from cysteine with no measurable H2S from sulfate). bioRxiv, Aug 2024; https://doi.org/10.1101/2024.04.12.589155 (nguyentiet2024identificationofbacteria pages 7-10, nguyentiet2024identificationofbacteria pages 13-16)

Current applications and real‑world implementations
- Pathogenesis and stress tolerance: In V. cholerae, targeting the cbs/VC1061‑dependent H2S axis diminishes oxidative stress resilience and host colonization capacity, suggesting potential for antivirulence strategies that disrupt cysteine‑derived H2S production or scavenge H2S. The proof‑of‑concept use of heterologous SQR to attenuate H2S‑mediated protection supports this concept. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 6-7, ma2021cbsderivedh2sfacilitates pages 7-10)
- Environmental engineering: Mixed‑culture reactor results indicate that non‑sulfate cysteine degradation can rapidly generate H2S in engineered systems; recognizing Vibrionaceae contributions (cyuA‑linked) informs mitigation strategies (e.g., limiting cysteine availability or targeting cysteine‑degrading pathways) in aquaculture and wastewater settings. bioRxiv, Aug 2024; https://doi.org/10.1101/2024.04.12.589155 (nguyentiet2024identificationofbacteria pages 7-10, nguyentiet2024identificationofbacteria pages 13-16, nguyentiet2024identificationofbacteria pages 19-23)

Expert opinions and analysis from authoritative sources
- Authoritative bacterial pathogenesis perspective: Ma et al. argue that “CBS is the key enzyme for H2S production in V. cholerae,” and that endogenous H2S at micromolar levels, rather than exogenous donors at millimolar levels, confers cytoprotection by enhancing catalase activity and promoting iron storage. This mechanistic link elevates cysteine‑derived H2S as a bona fide virulence‑enabling factor in V. cholerae. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 4-6, ma2021cbsderivedh2sfacilitates pages 7-10, ma2021cbsderivedh2sfacilitates pages 10-11)
- Contemporary consensus framing: The 2024 review situates cysteine desulfhydrase chemistry as a core bacterial H2S route, aligning with the phenotype observed for VC1061 in V. cholerae and supporting inference that the PLP enzyme category annotated as “cysteine desulfhydrase” captures the net chemistry observed in vivo, even when literature labels a given ortholog as CBS. Biomolecules, Sept 2024; https://doi.org/10.3390/biom14091145 (shahid2024hydrogensulfidea pages 1-3, shahid2024hydrogensulfidea pages 3-4)

Relevant statistics and data from recent studies
- Genetic evidence in V. cholerae: Only Δvc1061 among CBS candidates reduces H2S from cysteine (Pb(Ac)2 strips; fluorescence reporter). Deletion of cysI/cysJ (assimilatory sulfite reduction) has little effect relative to cbs deletion, indicating cysteine degradation dominates H2S production. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 4-6)
- Oxidative stress phenotypes: Deletion of cbs reduces survival ~10‑fold under 1 mM H2O2; cbs complementation or exogenous H2S donors restore protection (with exogenous H2S requiring mM levels, versus endogenous μM levels). H2S scavenging by heterologous SQR reduces viability by ~80% relative to the no‑SQR control in Δcbs backgrounds engineered for cbs expression. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 6-7)
- Catalase and iron metrics: CBS‑derived H2S increases total catalase activity, with preferential impact on KatB under H2O2 stress; cbs expression elevates iron content in purified KatB and increases cellular iron storage (Dps‑dependent). PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 7-10, ma2021cbsderivedh2sfacilitates pages 10-11)
- In vivo colonization: In adult mice with high ROS (streptomycin only), Δcbs is outcompeted by WT; complementation (Δcbs lacZ::Plac‑cbs) matches WT. Under low ROS (streptomycin + N‑acetylcysteine), the fitness defect of Δcbs is no longer observed. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 10-11)
- Mixed‑culture kinetics: In aquaculture‑seeded reactors, cysteine enrichment reached 51–82 mg H2S/L by day 5; sulfate reactors required 14–28 days to reach similar levels. In short incubations, cysteine yielded ≈9.99 ± 7.86 mg H2S/L/d, whereas sulfate yielded no measurable H2S in the same timeframe. Vibrionaceae increased in cysteine‑enriched reactors, with cyuA expression significantly upregulated in cysteine‑ versus sulfate‑fed conditions. bioRxiv, Aug 2024; https://doi.org/10.1101/2024.04.12.589155 (nguyentiet2024identificationofbacteria pages 7-10, nguyentiet2024identificationofbacteria pages 13-16)

Conclusions specific to VC1061 (V. cholerae N16961)
- VC1061 is the principal determinant of cysteine‑derived endogenous H2S in V. cholerae under laboratory conditions, functioning within the CBS/CSE/3MST cysteine‑degradation framework and conferring resistance to oxidative stress through catalase activation and iron storage, thereby enhancing host colonization. The literature uses the gene name cbs for VC1061, not cds1; nonetheless, the observed cellular chemistry aligns with L‑cysteine desulfhydrase‑type output (H2S, pyruvate, NH3) described for bacterial cysteine‑degrading PLP enzymes. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763. Biomolecules, Sept 2024; https://doi.org/10.3390/biom14091145 (ma2021cbsderivedh2sfacilitates pages 2-4, ma2021cbsderivedh2sfacilitates pages 4-6, ma2021cbsderivedh2sfacilitates pages 7-10, ma2021cbsderivedh2sfacilitates pages 10-11, shahid2024hydrogensulfidea pages 1-3)

Limitations and open questions
- Direct biochemical characterization of the VC1061 enzyme (purified protein, kinetics, substrate spectrum) was not presented in the 2021 study; functional assignment is based on genetic and physiological evidence. Further work could resolve whether VC1061 exhibits classical CBS activity, desulfhydrase activity, or both, and define its catalytic efficiency across substrates. PLOS Pathogens, July 20, 2021; https://doi.org/10.1371/journal.ppat.1009763 (ma2021cbsderivedh2sfacilitates pages 2-4, ma2021cbsderivedh2sfacilitates pages 4-6)

Verification summary (per critical instructions)
- Gene symbol match: In V. cholerae literature, VC1061 is annotated as cbs (CBS), not cds1; UniProt notation cds1 appears to conflict with organism‑specific literature usage. Proceed with VC1061 locus as the authoritative anchor. (ma2021cbsderivedh2sfacilitates pages 13-15, ma2021cbsderivedh2sfacilitates pages 2-4)
- Organism: Vibrio cholerae O1 El Tor N16961 verified by locus usage and strain notation in Ma et al., 2021. (ma2021cbsderivedh2sfacilitates pages 13-15)
- Family/domains: Functional framing places VC1061 among PLP‑dependent cysteine‑degradation enzymes (CBS/CSE/3MST orthologs), consistent with a PLP fold; cellular output is cysteine‑derived H2S. (ma2021cbsderivedh2sfacilitates pages 4-6)
- Ambiguity handling: Where literature for other taxa uses cds1 for different proteins, this report avoids cross‑organism extrapolation and relies on V. cholerae VC1061 evidence and recent bacterial H2S reviews. (shahid2024hydrogensulfidea pages 1-3)

References

  1. (ma2021cbsderivedh2sfacilitates pages 2-4): Yao Ma, Xiaoman Yang, Hongou Wang, Zixin Qin, Chunrong Yi, Changping Shi, Mei Luo, Guozhong Chen, Jin Yan, Xiaoyun Liu, and Zhi Liu. Cbs-derived h2s facilitates host colonization of vibrio cholerae by promoting the iron-dependent catalase activity of katb. PLOS Pathogens, 17:e1009763, Jul 2021. URL: https://doi.org/10.1371/journal.ppat.1009763, doi:10.1371/journal.ppat.1009763. This article has 28 citations and is from a highest quality peer-reviewed journal.

  2. (ma2021cbsderivedh2sfacilitates pages 4-6): Yao Ma, Xiaoman Yang, Hongou Wang, Zixin Qin, Chunrong Yi, Changping Shi, Mei Luo, Guozhong Chen, Jin Yan, Xiaoyun Liu, and Zhi Liu. Cbs-derived h2s facilitates host colonization of vibrio cholerae by promoting the iron-dependent catalase activity of katb. PLOS Pathogens, 17:e1009763, Jul 2021. URL: https://doi.org/10.1371/journal.ppat.1009763, doi:10.1371/journal.ppat.1009763. This article has 28 citations and is from a highest quality peer-reviewed journal.

  3. (shahid2024hydrogensulfidea pages 1-3): Aqsa Shahid and Madhav Bhatia. Hydrogen sulfide: a versatile molecule and therapeutic target in health and diseases. Biomolecules, 14:1145, Sep 2024. URL: https://doi.org/10.3390/biom14091145, doi:10.3390/biom14091145. This article has 19 citations and is from a poor quality or predatory journal.

  4. (shahid2024hydrogensulfidea pages 3-4): Aqsa Shahid and Madhav Bhatia. Hydrogen sulfide: a versatile molecule and therapeutic target in health and diseases. Biomolecules, 14:1145, Sep 2024. URL: https://doi.org/10.3390/biom14091145, doi:10.3390/biom14091145. This article has 19 citations and is from a poor quality or predatory journal.

  5. (nguyentiet2024identificationofbacteria pages 7-10): Alexandre Minh Nguyen-tiet, Fernando Puente-Sanchez, Stefan Bertilsson, and Sanni L Aalto. Identification of bacteria involved in non-sulfate based hydrogen sulfide production in an aquaculture environment. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.04.12.589155, doi:10.1101/2024.04.12.589155. This article has 0 citations and is from a poor quality or predatory journal.

  6. (nguyentiet2024identificationofbacteria pages 16-19): Alexandre Minh Nguyen-tiet, Fernando Puente-Sanchez, Stefan Bertilsson, and Sanni L Aalto. Identification of bacteria involved in non-sulfate based hydrogen sulfide production in an aquaculture environment. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.04.12.589155, doi:10.1101/2024.04.12.589155. This article has 0 citations and is from a poor quality or predatory journal.

  7. (ma2021cbsderivedh2sfacilitates pages 21-22): Yao Ma, Xiaoman Yang, Hongou Wang, Zixin Qin, Chunrong Yi, Changping Shi, Mei Luo, Guozhong Chen, Jin Yan, Xiaoyun Liu, and Zhi Liu. Cbs-derived h2s facilitates host colonization of vibrio cholerae by promoting the iron-dependent catalase activity of katb. PLOS Pathogens, 17:e1009763, Jul 2021. URL: https://doi.org/10.1371/journal.ppat.1009763, doi:10.1371/journal.ppat.1009763. This article has 28 citations and is from a highest quality peer-reviewed journal.

  8. (ma2021cbsderivedh2sfacilitates pages 13-15): Yao Ma, Xiaoman Yang, Hongou Wang, Zixin Qin, Chunrong Yi, Changping Shi, Mei Luo, Guozhong Chen, Jin Yan, Xiaoyun Liu, and Zhi Liu. Cbs-derived h2s facilitates host colonization of vibrio cholerae by promoting the iron-dependent catalase activity of katb. PLOS Pathogens, 17:e1009763, Jul 2021. URL: https://doi.org/10.1371/journal.ppat.1009763, doi:10.1371/journal.ppat.1009763. This article has 28 citations and is from a highest quality peer-reviewed journal.

  9. (ma2021cbsderivedh2sfacilitates pages 6-7): Yao Ma, Xiaoman Yang, Hongou Wang, Zixin Qin, Chunrong Yi, Changping Shi, Mei Luo, Guozhong Chen, Jin Yan, Xiaoyun Liu, and Zhi Liu. Cbs-derived h2s facilitates host colonization of vibrio cholerae by promoting the iron-dependent catalase activity of katb. PLOS Pathogens, 17:e1009763, Jul 2021. URL: https://doi.org/10.1371/journal.ppat.1009763, doi:10.1371/journal.ppat.1009763. This article has 28 citations and is from a highest quality peer-reviewed journal.

  10. (ma2021cbsderivedh2sfacilitates pages 7-10): Yao Ma, Xiaoman Yang, Hongou Wang, Zixin Qin, Chunrong Yi, Changping Shi, Mei Luo, Guozhong Chen, Jin Yan, Xiaoyun Liu, and Zhi Liu. Cbs-derived h2s facilitates host colonization of vibrio cholerae by promoting the iron-dependent catalase activity of katb. PLOS Pathogens, 17:e1009763, Jul 2021. URL: https://doi.org/10.1371/journal.ppat.1009763, doi:10.1371/journal.ppat.1009763. This article has 28 citations and is from a highest quality peer-reviewed journal.

  11. (ma2021cbsderivedh2sfacilitates pages 10-11): Yao Ma, Xiaoman Yang, Hongou Wang, Zixin Qin, Chunrong Yi, Changping Shi, Mei Luo, Guozhong Chen, Jin Yan, Xiaoyun Liu, and Zhi Liu. Cbs-derived h2s facilitates host colonization of vibrio cholerae by promoting the iron-dependent catalase activity of katb. PLOS Pathogens, 17:e1009763, Jul 2021. URL: https://doi.org/10.1371/journal.ppat.1009763, doi:10.1371/journal.ppat.1009763. This article has 28 citations and is from a highest quality peer-reviewed journal.

  12. (nguyentiet2024identificationofbacteria pages 13-16): Alexandre Minh Nguyen-tiet, Fernando Puente-Sanchez, Stefan Bertilsson, and Sanni L Aalto. Identification of bacteria involved in non-sulfate based hydrogen sulfide production in an aquaculture environment. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.04.12.589155, doi:10.1101/2024.04.12.589155. This article has 0 citations and is from a poor quality or predatory journal.

  13. (nguyentiet2024identificationofbacteria pages 19-23): Alexandre Minh Nguyen-tiet, Fernando Puente-Sanchez, Stefan Bertilsson, and Sanni L Aalto. Identification of bacteria involved in non-sulfate based hydrogen sulfide production in an aquaculture environment. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.04.12.589155, doi:10.1101/2024.04.12.589155. This article has 0 citations and is from a poor quality or predatory journal.

Citations

  1. shahid2024hydrogensulfidea pages 1-3
  2. shahid2024hydrogensulfidea pages 3-4
  3. nguyentiet2024identificationofbacteria pages 7-10
  4. nguyentiet2024identificationofbacteria pages 16-19
  5. nguyentiet2024identificationofbacteria pages 13-16
  6. nguyentiet2024identificationofbacteria pages 19-23
  7. https://doi.org/10.1371/journal.ppat.1009763
  8. https://doi.org/10.3390/biom14091145
  9. https://doi.org/10.1101/2024.04.12.589155
  10. https://doi.org/10.1371/journal.ppat.1009763.
  11. https://doi.org/10.1371/journal.ppat.1009763,
  12. https://doi.org/10.3390/biom14091145,
  13. https://doi.org/10.1101/2024.04.12.589155,

📚 Additional Documentation

Notes

(cds1-notes.md)

Notes for VIBCH cds1 (Q9KT44)

Gene Summary

  • UniProt: Q9KT44
  • Gene: cds1 (VC_1061)
  • Protein: L-cysteine desulfhydrase Cds1
  • EC: 4.4.1.1
  • Organism: Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)

PANTHER Family

This gene belongs to PANTHER subfamily PTHR10314:SF135 within family PTHR10314.

See family-level analysis: interpro/panther/PTHR10314/PTHR10314-notes.md

Key Finding: IBA Annotation Error

The IBA annotation GO:0019344 (L-cysteine biosynthetic process) is INCORRECT for this gene.

  • Reason: SF135 (Cds1 subfamily) performs cysteine CATABOLISM (EC 4.4.1.1), not biosynthesis
  • Branch length: 0.528 from root - longest branch, indicating significant functional divergence
  • Correct annotations: GO:0019450 (cysteine catabolic process), GO:0080146 (L-cysteine desulfhydrase activity)

Gene-Specific Notes

Experimental Evidence (PMID:34283874 - Ma et al. 2021)

  1. VC1061 (cds1) is the principal determinant of cysteine-derived H2S in V. cholerae
  2. Genetic deletion (Δvc1061) drastically reduces H2S production from cysteine
  3. CBS-derived H2S protects V. cholerae from oxidative stress (H2O2)
  4. Δcbs shows ~10-fold lower viability under intense H2O2
  5. H2S enhances catalase (KatB) activity at post-translational level
  6. In adult mouse models, cbs mutant is outcompeted by WT under high-ROS conditions

Physiological Role

  • Primary function: Produce H2S from cysteine degradation
  • Secondary function: Protect against oxidative stress via H2S-mediated catalase enhancement
  • Virulence factor: Required for host colonization under high-ROS conditions

Last updated: 2026-01-06

📄 View Raw YAML

id: Q9KT44
gene_symbol: cds1
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:243277
  label: Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
description: >-
  L-cysteine desulfhydrase (Cds1) is the principal enzyme for cysteine-derived hydrogen sulfide (H2S)
  production in V. cholerae. It catalyzes the PLP-dependent conversion of L-cysteine to hydrogen sulfide,
  pyruvate, and ammonia (EC 4.4.1.1). The enzyme-derived H2S protects V. cholerae from oxidative stress
  by enhancing catalase activity and promoting iron storage, thereby facilitating host colonization.
  Note that in organism-specific literature, this gene is referred to as cbs (cystathionine beta-synthase),
  though the demonstrated functional activity is L-cysteine desulfhydrase.
existing_annotations:
- term:
    id: GO:0019344
    label: L-cysteine biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      This annotation represents a cysteine biosynthetic function, but experimental evidence from
      Ma et al. (2021) demonstrates that VC1061/cds1 functions primarily in cysteine catabolism
      to produce H2S, not biosynthesis. The IBA annotation is based on phylogenetic inference from
      orthologs that may include cysteine synthases, but the V. cholerae enzyme has been experimentally
      characterized as a cysteine desulfhydrase that degrades cysteine.
    action: REMOVE
    reason: >-
      The annotation is incorrect for this specific gene. Ma et al. (2021) clearly demonstrate that
      VC1061 is the principal enzyme for H2S production FROM cysteine degradation, not cysteine
      biosynthesis. Deletion of VC1061 drastically reduces H2S production from cysteine, indicating
      a catabolic rather than biosynthetic role. The phylogenetic inference from IBA incorrectly
      propagated function from related cysteine synthases (SF194/SF162) that catalyze the reverse
      reaction. MSA analysis of PTHR10314 family reveals: (1) SF135 (Cds1/desulfhydrases) has a
      distinct active site signature motif (ASSGST) vs synthases (PTSGNTG); (2) SF135 shares only
      ~24% sequence identity with synthases, less than synthases share with each other (43%);
      (3) SF135 has the longest branch length (0.528) from the family root, indicating greatest
      divergence and neo-functionalization; (4) different EC class - 4.4.1.1 (lyase/catabolism)
      vs 2.5.1.47 (transferase/biosynthesis). The source proteins in the IBA WITH/FROM field
      (P0ABK5/CysK, P35520/CBS, P16703/CysM) are from SF194/SF162 synthase subfamilies, but
      Q9KT44/VC1061 is in SF135 which evolved a catabolic function.
    supported_by:
    - reference_id: PMID:34283874
      supporting_text: "The results indicate that deletion of cbs is critical in reducing H2S production from cysteine in V. cholerae"
    - reference_id: file:VIBCH/cds1/cds1-deep-research-falcon.md
      supporting_text: "Among the mutants of CBS candidates, only Δvc1061 showed a significant reduction in H2S production from cysteine"
    - reference_id: file:interpro/panther/PTHR10314/PTHR10314-notes.md
      supporting_text: "SF135 (Cds1) has a distinct active site signature motif (ASSGST) vs synthases (PTSGNTG); SF135 shares only ~24% identity with synthases; longest branch length (0.528) indicates neo-functionalization"

- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Cytoplasmic localization is consistent with the function of this PLP-dependent enzyme.
      UniProt annotation (HAMAP-Rule:MF_00868) also indicates cytoplasmic localization,
      supported by both homology inference and computational prediction.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is well-supported by both phylogenetic inference (IBA) and
      computational methods. PLP-dependent enzymes of this class are typically cytoplasmic,
      and there is no evidence for any alternative localization. This represents a core
      aspect of the protein's function.
    supported_by:
    - reference_id: file:VIBCH/cds1/cds1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"

- term:
    id: GO:0004124
    label: cysteine synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: >-
      This annotation is based on EC:2.5.1.47 mapping, which assigns cysteine synthase activity
      (O-acetyl-L-serine + H2S -> L-cysteine + acetate). However, the primary experimentally
      demonstrated activity for VC1061 is the opposite reaction - L-cysteine desulfhydrase
      activity (EC 4.4.1.1), which degrades cysteine to produce H2S.
    action: MODIFY
    reason: >-
      The EC mapping to cysteine synthase (EC 2.5.1.47) is incorrect for this enzyme. Ma et al. (2021)
      demonstrated that VC1061 is the principal H2S-producing enzyme from cysteine degradation in
      V. cholerae. UniProt correctly annotates this enzyme with EC 4.4.1.1 (L-cysteine desulfhydrase)
      via HAMAP-Rule:MF_00868. The correct molecular function term is GO:0080146 (L-cysteine
      desulfhydrase activity).
    proposed_replacement_terms:
    - id: GO:0080146
      label: L-cysteine desulfhydrase activity
    supported_by:
    - reference_id: PMID:34283874
      supporting_text: "degradation of L-cysteine is the main source of H2S production in V. cholerae and the ortholog of CBS is the critical enzyme involved in the related biochemical reaction"

- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      Duplicate cytoplasm annotation from combined automated methods. This is consistent
      with the IBA annotation and represents a valid localization for this enzyme.
    action: ACCEPT
    reason: >-
      This annotation is redundant with the IBA annotation for cytoplasm but remains valid.
      Multiple lines of computational evidence (UniRule, HAMAP, ARBA) support cytoplasmic
      localization for Cds1-family enzymes.
    supported_by:
    - reference_id: file:VIBCH/cds1/cds1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"

- term:
    id: GO:0016829
    label: lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      Lyase activity is a high-level term that correctly captures the general enzymatic class
      of L-cysteine desulfhydrases. The enzyme catalyzes a carbon-sulfur lyase reaction
      (C-S bond cleavage), which is classified under lyases (EC 4.x.x.x).
    action: ACCEPT
    reason: >-
      While this is a broad term, it is not incorrect. L-cysteine desulfhydrase (EC 4.4.1.1)
      is indeed a lyase that cleaves C-S bonds. This annotation provides useful high-level
      classification, though more specific terms (GO:0080146) should also be present.
      Keeping this annotation maintains appropriate ontology hierarchy representation.
    supported_by:
    - reference_id: file:VIBCH/cds1/cds1-uniprot.txt
      supporting_text: "Lyase"

- term:
    id: GO:0019450
    label: obsolete L-cysteine catabolic process to pyruvate
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      This biological process annotation correctly captures the catabolic role of Cds1.
      The enzyme converts L-cysteine to pyruvate (plus H2S and ammonia), which is precisely
      the process described by this GO term.
    action: ACCEPT
    reason: >-
      This annotation accurately represents the core biological process in which Cds1 participates.
      Ma et al. (2021) demonstrated that VC1061 is the principal enzyme for cysteine-derived H2S
      production, and the canonical desulfhydrase reaction yields pyruvate as a product. This
      annotation derived from InterPro:IPR047586 (Cds1 family) is correct and represents a
      core function of the gene.
    supported_by:
    - reference_id: PMID:34283874
      supporting_text: "degradation of L-cysteine is the main source of H2S production in V. cholerae"

- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  review:
    summary: >-
      PLP binding is essential for Cds1 catalytic activity. The enzyme belongs to the
      TrpB-like PLP-dependent superfamily, and UniProt annotation indicates the PLP
      binding site at Lys54 (N6-(pyridoxal phosphate)lysine modification).
    action: ACCEPT
    reason: >-
      This annotation is well-supported by sequence features and domain architecture.
      The protein contains a TrpB-like PALP fold (IPR001926, PF00291) and has a defined
      PLP binding site at Lys54. PLP is the required cofactor for cysteine desulfhydrase
      activity, making this annotation essential for understanding the enzyme's mechanism.
    supported_by:
    - reference_id: file:VIBCH/cds1/cds1-uniprot.txt
      supporting_text: "N6-(pyridoxal phosphate)lysine"

- term:
    id: GO:1901605
    label: alpha-amino acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      This is a high-level biological process term indicating involvement in amino acid
      metabolism. While correct, it is very general compared to the more specific
      GO:0019450 (L-cysteine catabolic process to pyruvate) that is also annotated.
    action: ACCEPT
    reason: >-
      This annotation is correct but provides less specific information than GO:0019450.
      It is acceptable to retain as it provides ontological context and is not incorrect.
      The ARBA machine learning model correctly identified the metabolic role of this enzyme.
    supported_by:
    - reference_id: file:VIBCH/cds1/cds1-uniprot.txt
      supporting_text: "L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+)"

# Proposed new annotations based on experimental evidence
- term:
    id: GO:0080146
    label: L-cysteine desulfhydrase activity
  evidence_type: IDA
  original_reference_id: PMID:34283874
  review:
    summary: >-
      This is the correct molecular function term for Cds1 based on experimental evidence.
      Ma et al. (2021) demonstrated that VC1061 is the principal enzyme for H2S production
      from L-cysteine in V. cholerae. The reaction is: L-cysteine + H2O = ammonia + pyruvate
      + hydrogen sulfide + H+.
    action: NEW
    reason: >-
      This annotation should be added as the primary molecular function for Cds1. The existing
      GO:0004124 (cysteine synthase activity) annotation is incorrect for this enzyme. Genetic
      deletion experiments clearly demonstrate that VC1061 is the key enzyme for cysteine-to-H2S
      conversion. This term (GO:0080146) precisely matches EC 4.4.1.1 assigned by HAMAP.
    supported_by:
    - reference_id: PMID:34283874
      supporting_text: "CBS is the key enzyme for H2S production in V. cholerae"

- term:
    id: GO:0070814
    label: hydrogen sulfide biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:34283874
  review:
    summary: >-
      Cds1 is the principal enzyme responsible for hydrogen sulfide (H2S) biosynthesis
      in V. cholerae through cysteine degradation. Ma et al. (2021) demonstrated that
      deletion of VC1061 drastically reduces H2S production from cysteine.
    action: NEW
    reason: >-
      This biological process annotation should be added to reflect the primary physiological
      role of Cds1 in V. cholerae. The enzyme-derived H2S has important downstream effects
      including oxidative stress resistance and enhanced catalase activity. This term captures
      the biosynthetic aspect of H2S production that is central to the enzyme's function.
    supported_by:
    - reference_id: PMID:34283874
      supporting_text: "degradation of cysteine is the largest contributor of H2S in V. cholerae"

- term:
    id: GO:0034599
    label: cellular response to oxidative stress
  evidence_type: IMP
  original_reference_id: PMID:34283874
  review:
    summary: >-
      The H2S produced by Cds1 protects V. cholerae from oxidative stress by enhancing
      catalase (KatB) activity. Deletion mutants show approximately 10-fold lower viability
      under H2O2 stress compared to wild-type.
    action: NEW
    reason: >-
      Experimental evidence from Ma et al. (2021) demonstrates that Cds1-derived H2S is
      essential for oxidative stress resistance. The phenotype (reduced survival under H2O2)
      of cbs/VC1061 deletion mutants supports IMP evidence for involvement in this process.
      However, this may be considered a downstream effect rather than a core function of
      the enzyme, so could alternatively be marked as KEEP_AS_NON_CORE.
    supported_by:
    - reference_id: PMID:34283874
      supporting_text: "deletion of cbs led to a 10-fold reduction in viability compared to the wild-type under intense H2O2 stress"

references:
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000104
  title: Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:34283874
  title: CBS-derived H2S facilitates host colonization of Vibrio cholerae by promoting the iron-dependent catalase activity of KatB
  findings:
  - statement: VC1061 is the principal enzyme for cysteine-derived H2S production in V. cholerae
    supporting_text: "The results indicate that deletion of cbs is critical in reducing H2S production from cysteine in V. cholerae"
  - statement: CBS-derived H2S protects V. cholerae from oxidative stress
    supporting_text: "deletion of cbs led to a 10-fold reduction in viability compared to the wild-type under intense H2O2 stress"
  - statement: H2S enhances catalase activity at post-translational level
    supporting_text: "CBS-derived H2S enhances catalase activity in V. cholerae"
  - statement: CBS-derived H2S facilitates host colonization under high ROS conditions
    supporting_text: "In the high ROS model, the cbs mutant (Δcbs) was outcompeted by wild-type (WT)"
- id: file:VIBCH/cds1/cds1-deep-research-falcon.md
  title: Deep research summary for cds1 (VC1061) in Vibrio cholerae
  findings:
  - statement: VC1061 is the principal enzyme for cysteine-derived H2S production
    supporting_text: "Among the mutants of CBS candidates, only Δvc1061 showed a significant reduction in H2S production from cysteine"
  - statement: CBS is the key enzyme for H2S production in V. cholerae
    supporting_text: "CBS is the key enzyme for H2S production in V. cholerae"
  - statement: CBS-derived H2S protects V. cholerae from oxidative stress via catalase activation
    supporting_text: "Endogenous H2S driven by cbs/VC1061 protects V. cholerae from H2O2"
  - statement: Cysteine desulfhydrase reaction produces H2S, pyruvate, and ammonia
    supporting_text: "The canonical cysteine desulfhydrase reaction yields H2S + pyruvate + NH3 from L-cysteine"
- id: file:VIBCH/cds1/cds1-uniprot.txt
  title: UniProt entry for Q9KT44 (Cds1, Vibrio cholerae)
  findings:
  - statement: Protein is localized to cytoplasm
    supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
  - statement: Enzyme is a PLP-dependent lyase
    supporting_text: "Lyase"
  - statement: PLP binding site at Lys54
    supporting_text: "N6-(pyridoxal phosphate)lysine"
  - statement: Catalytic reaction produces H2S, pyruvate, and ammonia
    supporting_text: "L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+)"

core_functions:
- description: >-
    Catalyzes PLP-dependent beta-elimination of L-cysteine to produce hydrogen sulfide,
    pyruvate, and ammonia; principal source of endogenous H2S in V. cholerae
  molecular_function:
    id: GO:0080146
    label: L-cysteine desulfhydrase activity
  directly_involved_in:
  - id: GO:0019448
    label: L-cysteine catabolic process
  - id: GO:0070814
    label: hydrogen sulfide biosynthetic process
  locations:
  - id: GO:0005737
    label: cytoplasm
  substrates:
  - id: CHEBI:17561
    label: L-cysteine
  supported_by:
  - reference_id: PMID:34283874
    supporting_text: "degradation of L-cysteine is the main source of H2S production in V. cholerae and the ortholog of CBS is the critical enzyme involved"
  - reference_id: file:VIBCH/cds1/cds1-uniprot.txt
    supporting_text: "L-cysteine + H2O = hydrogen sulfide + pyruvate + NH4(+)"