EryCIII (SACE_0726) is the desosaminyl glycosyltransferase (EC 2.4.1.278) of erythromycin biosynthesis in Saccharopolyspora erythraea. It transfers D-desosamine from the nucleotide sugar donor TDP-D-desosamine onto 3-alpha-mycarosylerythronolide B, converting it to erythromycin D, and is highly active and selective for its natural donor and macrolide acceptor (PMID:15303858). EryCIII works in concert with its activating partner EryCII, with which it forms an elongated heterotetramer; EryCII stabilizes and allosterically activates the glycosyltransferase (PMID:22056329; PDB 2YJN). EryCIII is a member of the GT-B superfamily desosaminyl transferase family.
Definition: Catalysis of the transfer of D-desosamine from TDP-D-desosamine to 3-alpha-mycarosylerythronolide B, producing erythromycin D and TDP. Corresponds to EC 2.4.1.278.
Justification: EC 2.4.1.278 has no specific GO molecular function term; EryCIII is currently annotated only with the general parents (glycosyltransferase / hexosyltransferase activity). A specific term would precisely capture this characterized activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008194 UDP-glycosyltransferase activity | IEA GO_REF:0000002 | REMOVE | Summary: InterPro-based (IEA) UDP-glycosyltransferase activity. EryCIII uses TDP-D-desosamine, a dTDP-sugar, as its donor (PMID:15303858), not a UDP-sugar, so the UDP-specific term is incorrect. The accurate activity is hexosyltransferase (already IDA-supported below). Reason: Wrong donor specificity (TDP-D-desosamine, a dTDP-sugar, not a UDP-sugar). The accurate term GO:0016758 (hexosyltransferase activity) is already present (IEA + IDA), so this incorrect UDP-specific term should be removed rather than modified into a duplicate. Supporting Evidence: PMID:15303858 EryCIII converts alpha-mycarosyl erythronolide B into erythromycin D using TDP-d-desosamine as the glycosyl donor. |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA general glycosyltransferase activity. Correct broad parent of the desosaminyl transferase reaction. Reason: Accurate general molecular function (true parent of the specific activity). Supporting Evidence: PMID:15303858 a new desosaminyl transferase, EryCIII |
| GO:0016758 hexosyltransferase activity | IEA GO_REF:0000117 | ACCEPT | Summary: IEA hexosyltransferase activity (orthology). Accurate for the desosaminyl (deoxyhexose) transfer; also experimentally supported (IDA) below. Reason: Accurate molecular function, corroborated by direct experimental evidence. Supporting Evidence: PMID:15303858 EryCIII converts alpha-mycarosyl erythronolide B into erythromycin D using TDP-d-desosamine as the glycosyl donor. |
| GO:0017000 antibiotic biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: IEA antibiotic biosynthetic process. Correct (erythromycin is an antibiotic) but general; the more specific GO:1901115 (erythromycin biosynthetic process) is available and is captured in core_functions. Reason: Accurate biological process; retained. A more specific child term (GO:1901115 erythromycin biosynthetic process) is proposed as the core annotation rather than replacing this correct general term. Supporting Evidence: PMID:15303858 EryCIII converts alpha-mycarosyl erythronolide B into erythromycin D |
| GO:0016758 hexosyltransferase activity | IDA PMID:15303858 Reconstitution and characterization of a new desosaminyl tra... | ACCEPT | Summary: Direct experimental (IDA) hexosyltransferase activity from in vitro reconstitution of EryCIII (kcat > 100 min-1, selective for TDP-D-desosamine). Reason: Core molecular function with direct experimental support; the defining catalytic activity of EryCIII (EC 2.4.1.278). Supporting Evidence: PMID:15303858 The enzyme was found to be highly active with a kcat greater than 100 min-1 |
| GO:0017000 antibiotic biosynthetic process | IDA PMID:15303858 Reconstitution and characterization of a new desosaminyl tra... | ACCEPT | Summary: Direct experimental (IDA) involvement in antibiotic (erythromycin) biosynthesis: EryCIII produces erythromycin D from alpha-mycarosyl erythronolide B. Reason: Core biological process with experimental support. (The more specific GO:1901115 erythromycin biosynthetic process is proposed as the replacement for the IEA duplicate above and is captured in core_functions.) Supporting Evidence: PMID:15303858 EryCIII converts alpha-mycarosyl erythronolide B into erythromycin D |
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Download this section (compressed HTML)Q: Per GO guidelines the desosaminyltransferase activity (EC 2.4.1.278) is annotated to the catalytic member EryCIII (enables), with EryCII captured separately as enzyme activator activity and both as subunits of the protein-containing complex. Given that EryCIII is inactive without EryCII, is an additional contributes_to from EryCII to the GT activity warranted?
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