fosB encodes a divalent-metal-dependent fosfomycin resistance enzyme in Staphylococcus aureus. FosB catalyzes thiol-dependent ring opening of fosfomycin, preferentially using bacillithiol in staphylococci, to form an inactive fosfomycin-thiol conjugate. This is mechanistically distinct from FosA glutathione transferases and FosX hydrolases.
Definition: Catalysis of the addition of bacillithiol or a related low-molecular-mass thiol to fosfomycin, opening the fosfomycin epoxide ring and forming an inactive fosfomycin-thiol conjugate.
Justification: FosB enzymes are not glutathione transferases, and propagation of a generic FosA/GST mapping would mis-annotate staphylococcal FosB. A FosB-specific GO term is needed to represent bacillithiol/L-cysteine-dependent fosfomycin inactivation.
Parent term: transferase activity, transferring alkyl or aryl (other than methyl) groups
Mappings:
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Correct cofactor annotation, but secondary to the fosfomycin thiol-transferase activity. Reason: UniProt and the FosB mechanism paper support divalent-metal dependence. The binding term should not be treated as the core function. Supporting Evidence: file:genes/STAAT/fosB/fosB-uniprot.txt Name=Mg(2+) PMID:23256780 FosB is a divalent-metal-dependent thiol-S-transferase implicated in fosfomycin |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Correct location for a soluble staphylococcal fosfomycin-inactivation enzyme. Reason: The UniProt record carries cytoplasm as the subcellular-location-derived GO annotation. Supporting Evidence: file:genes/STAAT/fosB/fosB-uniprot.txt DR GO; GO:0005737; C:cytoplasm |
| GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups | IEA GO_REF:0000120 | ACCEPT | Summary: Directionally correct core MF, but far less specific than the needed FosB/fosfomycin thiol-S-transferase term. Reason: FosB catalyzes transfer/addition of a thiol cofactor to fosfomycin. GO lacks a suitable fosfomycin-specific bacillithiol/L-cysteine transferase term, so the broad transferase term is retained while a new term is proposed. Supporting Evidence: file:genes/STAAT/fosB/fosB-uniprot.txt Metallothiol transferase which confers resistance to PMID:23256780 SaFosB is the first to be characterized among a new class of enzyme |
| GO:0046677 response to antibiotic | IEA GO_REF:0000120 | ACCEPT | Summary: Correct high-level antibiotic-response annotation for a fosfomycin-inactivation enzyme. Reason: FosB is a bona fide antibiotic-inactivation resistance determinant, although the most useful curation gain is the specific molecular function. Supporting Evidence: file:genes/STAAT/fosB/fosB-uniprot.txt DR CARD; ARO:3004661; Saur_FosB; ARO:0001004; antibiotic inactivation. PMID:23256780 Disruption of BSH biosynthesis in S. aureus increases sensitivity to fosfomycin. |
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Download this section (compressed HTML)Q: Should GO model FosB as a bacillithiol-specific term, a broader fosfomycin thiol-S-transferase term, or both?
Experiment: Compare purified FosB activity with bacillithiol, L-cysteine, glutathione, and coenzyme A across representative FosB subfamilies to set the substrate scope for the GO term.
Type: in vitro enzyme assay
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