Notes: benzil reductase (EC 1.1.1.320 / RHEA:25968) gene set

Reviewed as a set with the other UniProt entries carrying RHEA:25968: yeast IRC24 and NRE1, B. cereus yueD (Q8RJB2), B. subtilis yueD (O32099). Gerbil SPR (Q8R536) also carries RHEA:25968, but it is a sepiapterin reductase that was incidentally tested on benzil, so it is out of scope.

Why this set was reviewed

GO:0102306 "benzil reductase [(S)-benzoin-forming] activity" was obsoleted
(geneontology/go-ontology#30498, "not a physiologically relevant substrate"), and
RHEA:25968 was then attached as a skos:narrowMatch to the EC 1.1.1.- grouping
class GO:0016616. Consequences visible in GOA:

• The experimental benzil annotations (SGD IDA PMID:37602278; UniProt EXP
  PMID:11796169, PMID:11745140) now sit on GO:0016616, which only says "CH-OH
  donor, NAD(P) acceptor".
• New IEA rows (GO_REF:0000120, 2026-07-27, with/from RHEA:25968) are generated
  to the same grouping class.

Biology

• B. cereus YueD: found by expression screen; NADPH-dependent stereospecific benzil ->
  (S)-benzoin; broad aromatic carbonyl specificity (diketones, 1,4-naphthoquinone,
  p-nitrobenzaldehyde); GFP shows cytoplasm PMID:11796169.
• Yeast Irc24 (YIR036C) and its tandem paralog Nre1 (YIR035C, 52% identical) both reduce benzil and
  prefer NADPH 2:1 over NADH PMID:37602278.
• All substrates are xenobiotic; no physiological substrate is known for any member.
• Sister reaction RHEA:31891 (1-phenyl-1,2-propanedione, also EC 1.1.1.320) is
  already narrowMatch to GO:0004090 carbonyl reductase (NADPH) activity, which yields the
  GO_REF:0000116 IEA to GO:0004090 on IRC24 and on B. cereus YueD.

Decisions

• GO:0016616 rows -> MODIFY to GO:0004090. (S)-benzoin is a secondary alcohol, and
  benzil -> benzoin is ketone -> secondary alcohol with NADPH: exactly the
  GO:0004090/EC 1.1.1.184 reaction. EC 1.1.1.184's synonym list includes "xenobiotic ketone reductase".
• GO:0050664 (NAD(P)H, O2 acceptor) on IRC24 (SGD IDA 2013) and its IBA onto NRE1
  -> MODIFY to GO:0004090; the acceptor is benzil, not O2.
• Bacillus sepiapterin reductase / BH4 biosynthesis (PTHR44085 IBA/IEA): BH4
  process REMOVE (pathway absent in Bacillus); SPR activity over-annotated or
  undecided (never tested).
• No new GO term is needed: a benzil-specific term would reverse #30498, and
  GO:0004090 already covers the reaction class.

Proposed GO-side change

Move xref: RHEA:25968 {source="skos:narrowMatch"} from GO:0016616 to GO:0004090.
More generally, flag any RHEA xref on an EC-incomplete (x.x.x.-) grouping term:
currently 9 reactions on GO:0016616, GO:0008241 and GO:0016712.

Gene-specific notes: IRC24 (P40580, YIR036C)

The set-level notes above are shared across the four RHEA:25968 genes. What is
specific to this one:

• It is the founding yeast member. Maruyama et al. isolated the gene and
  showed the recombinant protein reduces benzil
  PMID:11796169,
  which is also the quote now used for the GO:0004090 and GO:0016616 rows. An
  earlier draft of this review supported those rows with the paper's B. cereus
  sentence; that was a cross-organism citation and was corrected after PR review.
• It is the IBA seed. The GO:0050664 IBA on NRE1 is seeded from this gene's
  own SGD IDA (SGD:S000001475) via PANTHER:PTN002453021. Per the project's IBA
  guidance that self-appearance in WITH/FROM is correct and expected, not
  circular, so it is deliberately not marked CIRCULAR_OR_REDUNDANT.
• The GO:0050664 problem originates here. The 2013 SGD IDA chose a term
  whose EC 1.6.3.- acceptor is molecular oxygen, while the assay reduces benzil
  with NADPH. The citation is correct in every respect; only the term is wrong.
  The propagation_review therefore records root_cause TERM_SCOPING_PROBLEM and
  asserts no failure_modes, since no enum value describes a wrong-acceptor term.
• Two process-level hints that go nowhere. Deletion raises spontaneous Rad52
  focus levels [UniProt DISRUPTION PHENOTYPE, ECO:0000269|PubMed:18085829], and
  the gene is induced by single-strand DNA damage
  [UniProt INDUCTION, ECO:0000269|PubMed:17163986 - a genome-wide transcriptional
  response study, not an IRC24-specific one]. Neither connects the reductase
  chemistry to genome maintenance, so the ND biological_process row is accepted
  rather than replaced.
• Kinetics. Km 0.42 mM for benzil with NADPH, 1.2 mM with NADH; kcat
  9.2 min-1 on benzil and 86.2 min-1 on 1-phenyl-1,2-propanedione (UniProt
  BIOPHYSICOCHEMICAL PROPERTIES). The ~9x faster turnover on the smaller
  aryl-alkyl diketone is the same affinity/efficiency split the OpenScientist
  run later found for B. cereus YueD.