yueD

Summary: Rhea-mapping IEA from RHEA:31891 (1-phenyl-1,2-propanedione reduction); the most informative existing MF term for this broad-specificity NADPH carbonyl reductase.

Reason: The protein reduces aryl alpha-diketones (benzil, 1-phenyl-1,2-propanedione) to secondary alcohols with NADPH. That is the reaction class of GO:0004090 (EC 1.1.1.184). The physiological substrate is unknown, which is consistent with this broad term rather than a substrate-specific one.

Summary: TreeGrafter IEA to sepiapterin reductase, from PTHR44085 membership.

Reason: Sepiapterin reductase is the terminal enzyme of tetrahydrobiopterin (BH4) synthesis. YueD's sequence identity to mammalian SPR is only 28-30%. Its measured substrates are aromatic diketones, quinones and aldehydes, and sepiapterin itself has never been tested. Family membership alone does not establish pterin specificity across this low-identity bacterial branch.

Summary: GFP-tagged YueD localizes to the (bipolar) cytoplasm in B. cereus.

Reason: Direct localization in the native organism.

Summary: Keyword-mapped cytoplasm location; consistent with a soluble SDR lacking targeting signals.

Reason: Soluble SDR-family reductase with no signal peptide or transmembrane segment; cytoplasm is supported experimentally for B. cereus YueD (GFP) and yeast Nre1/Irc24.

Summary: TreeGrafter IEA to tetrahydrobiopterin biosynthesis.

Reason: BH4 biosynthesis is an animal pathway (GTP cyclohydrolase I, PTPS, SPR), and there is no evidence that Bacillus synthesizes BH4. This is family-level pathway transfer that ignores organism context (PATHWAY_CONTEXT_IGNORED).

Summary: Expression screen: clone conferring benzil -> (S)-benzoin reduction.

Reason: The assay (NADPH-dependent reduction of the diketone benzil to the secondary alcohol (S)-benzoin) is sound, but GO:0016616 is the EC 1.1.1.- grouping class and says only that some CH-OH/NAD(P) oxidoreduction occurs. The specific term GO:0102306 benzil reductase [(S)-benzoin-forming] activity was obsoleted (go-ontology#30498) because benzil is not a physiological substrate, and annotations were moved up to this grouping term. The reaction is, however, an instance of GO:0004090 carbonyl reductase (NADPH) activity (a secondary alcohol + NADP+ = a ketone + NADPH + H+; EC 1.1.1.184, whose synonyms explicitly include xenobiotic ketone reductase). GO already maps the sister EC 1.1.1.320 reaction RHEA:31891 (1-phenyl-1,2-propanedione) to GO:0004090. GO:0004090 is the informative term that respects the obsoletion decision; no new benzil-specific term is warranted.

Proposed replacements: carbonyl reductase (NADPH) activity

Summary: Recombinant YueD reduces benzil to (S)-benzoin with NADPH in vitro.

Reason: The assay (NADPH-dependent reduction of the diketone benzil to the secondary alcohol (S)-benzoin) is sound, but GO:0016616 is the EC 1.1.1.- grouping class and says only that some CH-OH/NAD(P) oxidoreduction occurs. The specific term GO:0102306 benzil reductase [(S)-benzoin-forming] activity was obsoleted (go-ontology#30498) because benzil is not a physiological substrate, and annotations were moved up to this grouping term. The reaction is, however, an instance of GO:0004090 carbonyl reductase (NADPH) activity (a secondary alcohol + NADP+ = a ketone + NADPH + H+; EC 1.1.1.184, whose synonyms explicitly include xenobiotic ketone reductase). GO already maps the sister EC 1.1.1.320 reaction RHEA:31891 (1-phenyl-1,2-propanedione) to GO:0004090. GO:0004090 is the informative term that respects the obsoletion decision; no new benzil-specific term is warranted.

Proposed replacements: carbonyl reductase (NADPH) activity

Summary: Combined IEA driven by RHEA:25968 mapped to the EC 1.1.1.- grouping class.

Reason: This IEA is generated from the RHEA:25968 narrowMatch xref on the grouping class GO:0016616, which was added when GO:0102306 was obsoleted. It is not wrong, but it is uninformative; a RHEA reaction mapped to an EC-incomplete grouping class yields annotations that say nothing about substrate class. Replace with GO:0004090 (and fix the xref upstream: RHEA:25968 should be a narrowMatch of GO:0004090, as its sister reaction RHEA:31891 already is).

Proposed replacements: carbonyl reductase (NADPH) activity