eryCIII (A4F7P3, SACE_0726) — review notes

Part of the BGC exemplar curation project (projects/BGC.md). MIBiG BGC0000055
(Saccharopolyspora erythraea, erythromycin PKS). GenBank CAM00067.1 → UniProt
A4F7P3 (ERYC3_SACEN), gene eryCIII / SACE_0726.

Function — the desosaminyl glycosyltransferase

EryCIII is the TDP-D-desosamine glycosyltransferase (EC 2.4.1.278) of erythromycin
biosynthesis; it is the catalytic partner of the activator EryCII.

• "EryCIII converts alpha-mycarosyl erythronolide B into erythromycin D using
  TDP-d-desosamine as the glycosyl donor... highly active with a kcat greater than
  100 min-1... selective for the natural nucleotide sugar donor and macrolide
  acceptor." [PMID:15303858 — IDA source]
• "the glycosyltransferase (GT) EryCIII, in concert with its partner EryCII, attaches
  a nucleotide-activated sugar to the macrolide scaffold with high specificity";
  heterotetramer with EryCII (PDB 2YJN). PMID:22056329

Annotation issues

• GO:0008194 UDP-glycosyltransferase activity (IEA) → MODIFY → GO:0016758
  hexosyltransferase activity. The donor is TDP-D-desosamine, not a UDP-sugar,
  so the UDP-specific term is incorrect; the accurate activity is already IDA-supported.
• GO:0017000 antibiotic biosynthetic process (IEA + IDA) → ACCEPT (correct; erythromycin
  is an antibiotic); add the more specific GO:1901115 erythromycin biosynthetic
  process as the core BP (IDA-supported by PMID:15303858).
• GO:0016757 glycosyltransferase activity (IEA) → ACCEPT (true general parent).
• GO:0016758 hexosyltransferase activity (IEA + IDA) → ACCEPT (accurate; IDA).
• GO:0017000 antibiotic biosynthetic process (IDA) → ACCEPT (experimental; erythromycin
  is an antibiotic).

No GO MF term exists for EC 2.4.1.278 specifically → candidate proposed_new_term.

Literature nuance (from PMID:22056329 full text)

The 2012 structure study found purified EryCIII inactive on its own, with activity
restored only by EryCII ("EryCII is required by EryCIII"), whereas the 2004 IDA paper
(PMID:15303858) reported high standalone activity (kcat > 100 min⁻¹). Reconciliation:
EryCIII is the catalytic (hexosyltransferase) subunit, but reliable activity is realized
in the α2β2 EryCIII·EryCII complex — supporting annotating the catalysis to the complex
with EryCII contributing GO:0008047 enzyme activator activity.

Predicted-complex evidence (BGC project)

Moriwaki et al. (bioRxiv 2025.10.26.684697) predict the EryCII-EryCIII interaction
(BGC0000055; CAM00066.1/CAM00067.1) at ipTM 0.92, matching PDB 2YJN.

References

• PMID:15303858 — Lee et al. 2004, JACS (EryCIII reconstitution; TDP-D-desosamine
  donor; IDA). VERIFIED.
• PMID:22056329 — Moncrieffe et al. 2012, J Mol Biol (EryCIII·EryCII structure, 2YJN). VERIFIED.