Ergothioneine Biosynthesis Variant-Pathway Terms — Obsoletion

SCOPING OBSOLETION

Species: MYCS2

Ergothioneine Biosynthesis Variant-Pathway Terms — Obsoletion

Bottom line: GO has retired the two route-specific children of
GO:0052699 ergothioneine biosynthetic process: the bacterial route
GO:0052704 (via gamma-glutamyl-hercynylcysteine sulfoxide) and the fungal
route GO:0140479. Which intermediates a pathway passes through is detail
GO now leaves to MetaCyc and GO-CAMs, so all annotations move to the
parent. We checked the affected annotations: four IDA rows, one per enzyme
of the Mycolicibacterium smegmatis egtBCDE operon, all from
PMID:20420449, plus about 2,247 IEA rows that migrate automatically. Both
children are now obsolete (OLS lists GO:0052704 as obsolete, so the
"still active" notes below predate that). No review in this repo uses any
of the three terms, and none of the egt genes is reviewed. Scoped, not
yet started: the four-enzyme operon is a compact batch to add if the repo
wants mycobacterial pathway coverage.

Overview

A GO obsoletion retires the two variant-pathway children of
GO:0052699 ergothioneine biosynthetic process. These children encode
how ergothioneine is made (bacterial vs fungal route), which is a
level of pathway-variant detail that upstream curators have decided is
beyond GO scope (better captured by MetaCyc pathways or GO-CAMs). All
affected annotations move to the parent term.

Both replaced by:

Per the upstream ontology decision, the two MetaCyc variant pathways
(MetaCyc:PWY-7255 ergothioneine biosynthesis I (bacteria) and
MetaCyc:PWY-7550 ergothioneine biosynthesis II (fungi)) are added as
narrowMatch cross-references on GO:0052699 rather than being
preserved as distinct GO classes.

This project tracks the impact on AI Gene Review. No genes in scope are
currently reviewed here.

Upstream tickets

Obsoletion plan (per upstream)

Obsoleted term ID Status Replacement
ergothioneine biosynthesis ... via gamma-glutamyl-hercynylcysteine sulfoxide GO:0052704 active (migration pending) GO:0052699 ergothioneine biosynthetic process
ergothioneine biosynthesis ... via hercynylcysteine sulfoxide synthase GO:0140479 already obsolete GO:0052699 ergothioneine biosynthetic process

The fungal-route term GO:0140479 carried zero direct experimental
annotations, so it was obsoleted directly. The bacterial-route term
GO:0052704 is still active because the four UniProt experimental
annotations (plus a large IEA pool) must be migrated to GO:0052699
before it can be retired — that migration is what go-annotation#6402
tracks.

Affected experimental annotations (verified via QuickGO 2026-05-21)

All four direct experimental annotations are to GO:0052704, all on
genes of the Mycolicibacterium smegmatis mc(2)155 egt operon, all
IDA (ECO:0000314), all from the same study (PMID:20420449, the in vitro
reconstitution of the mycobacterial ergothioneine pathway), all
assigned by UniProt, qualifier involved_in.

Gene UniProt Locus Protein name Taxon
egtB A0R5N0 MSMEG_6249 Hercynine oxygenase (sulfoxide synthase) NCBITaxon:246196
egtC A0R5M9 MSMEG_6248 Gamma-glutamyl-hercynylcysteine sulfoxide hydrolase NCBITaxon:246196
egtD A0R5M8 MSMEG_6247 Histidine N-alpha-methyltransferase NCBITaxon:246196
egtE A0R5M7 MSMEG_6246 Hercynylcysteine sulfoxide lyase NCBITaxon:246196

NCBITaxon:246196 = Mycolicibacterium smegmatis (strain ATCC 700084 /
mc(2)155); UniProt mnemonic suffix MYCS2.

Each annotation simply moves to GO:0052699 ergothioneine
biosynthetic process — the obsoletion is terminological, not a change
of biology. The four enzymes catalyze consecutive steps of the same
pathway, so the parent BP term is the correct shared placement.

IEA pool (auto-migrated)

GO:0052704 also carries roughly 2,247 IEA annotations (mostly
egtB orthologs across bacteria) assigned via GO_REF:0000108
(automatic logical inference). These will be regenerated against
GO:0052699 automatically once GO:0052704 is obsoleted and the inference
pipeline re-runs — no per-annotation work is needed here.

Parent-term annotations (unaffected)

GO:0052699 already carries 2 direct experimental annotations —
Schizosaccharomyces pombe egt1 (O94632) and egt2 (O94431), both
IMP from PMID:24828577. These are on the surviving parent term and are
not affected by the obsoletion.

Impact on this repo

No genes annotated to GO:0052704 or GO:0140479 are currently reviewed
in this repo:

So no existing review needs a refresh for the obsoletion itself.
The opportunity is that the M. smegmatis egt operon is a compact,
well-characterized four-enzyme biosynthetic pathway with no coverage in
this repo, and the obsoletion is a natural trigger to add it.

Scope

Candidate genes for initial review

Verify each with just fetch-gene MYCS2 <gene> before starting and
confirm UniProt accessions. Species folder: use MYCS2, not the
existing MYCSM. The four accessions are strain mc(2)155 entries
(e.g. EGTB_MYCS2, A0R5N0, taxon 246196), and the repo already files
strain-specific UniProt mnemonics beside generic ones (PSEAE beside
PSEAI, ECOLI beside ECOLX). MYCSM is the generic taxon-1772 code
used by the arr review. None are currently in the repo. The four
genes form one operon and are best reviewed together as a small batch.

Tier 1 — direct experimental annotation, well-characterized

  1. egtD / A0R5M8 (MSMEG_6247) — histidine N-alpha-methyltransferase;
    catalyzes the first committed step, SAM-dependent triple methylation
    of L-histidine to hercynine. The cognate MF (a histidine
    N-methyltransferase activity) should anchor the review; BP anchors on
    GO:0052699 post-obsoletion.
  2. egtB / A0R5N0 (MSMEG_6249) — hercynine oxygenase / sulfoxide
    synthase; the signature non-heme-iron enzyme that forms the C–S bond
    between hercynine and cysteine (or gamma-glutamylcysteine). Most
    mechanistically studied step of the pathway.
  3. egtC / A0R5M9 (MSMEG_6248) — gamma-glutamyl-hercynylcysteine
    sulfoxide hydrolase; a glutamine-amidotransferase-class enzyme that
    removes the gamma-glutamyl group.
  4. egtE / A0R5M7 (MSMEG_6246) — hercynylcysteine sulfoxide lyase;
    PLP-dependent C–S lyase that produces ergothioneine in the final
    step.

All four are characterized in PMID:20420449 (Seebeck FP, 2010, J Am
Chem Soc — in vitro reconstitution of mycobacterial ergothioneine
biosynthesis), which is the single reference behind every affected
annotation.

Tier 2 — opportunistic, fungal route

  1. egt1 / O94632 and egt2 / O94431 (S. pombe) — already
    annotated to the surviving parent GO:0052699; not affected by the
    obsoletion. Reviewing them would extend SCHPO coverage but is not
    required by this ticket.

Proposed approach

  1. Fungal obsoletion has already landed (GO:0140479 is obsolete);
    the bacterial-route obsoletion (GO:0052704) is pending the
    annotation migration tracked in the still-open go-annotation#6402.
    The replacement target is unambiguous (the parent GO:0052699), so
    reviews can proceed now and simply anchor BP on GO:0052699.
  2. Review the four M. smegmatis egt genes as one batch. Run
    just fetch-gene MYCS2 egtD (and egtB/egtC/egtE), then /review
    per CLAUDE.md. Because the four enzymes share one pathway and one
    reference (PMID:20420449), the literature work is largely shared.
  3. For each gene, anchor on the cognate molecular function — the
    pathway membership (GO:0052699) is the BP; the per-enzyme catalytic
    activity (methyltransferase, oxygenase/sulfoxide synthase,
    amidotransferase/hydrolase, C–S lyase) is the more informative MF
    and should drive core_functions. Look up precise MF terms via the
    OLS MCP rather than guessing IDs.
  4. Do not create reviews for the ~2,247 IEA egtB orthologs — they
    are auto-migrated by the logical-inference pipeline.
  5. Defer the S. pombe egt1/egt2 pair unless SCHPO ergothioneine
    coverage is wanted independently; they are on the surviving parent
    term and unaffected.

Priority

Low-medium. Only four direct experimental annotations are affected
and the migration is mechanical (variant-pathway term collapsed to its
parent). No existing review in this repo is blocked. The opportunity —
not the urgency — is that the M. smegmatis egt operon is a clean,
fully reconstituted four-enzyme pathway with a single well-cited
reference and no coverage here, making it an efficient small batch if
the repo wants to extend Mycolicibacterium coverage.

Status

Slides