Msed_0147 (A4YD22) notes: biotin carboxylase (alpha) subunit of acetyl-CoA/propionyl-CoA carboxylase

Automated deep research was unavailable for this gene (no -deep-research-*.md file). These notes
come from my own literature search (Europe PMC, cached papers in publications/) and the UniProt
record. Session date 2026-11-01.

Identity

• UniProt A4YD22 (TrEMBL, unreviewed), 510 aa, "Biotin carboxylase", EC 6.3.4.14, locus Msed_0147.
• Domains: biotin carboxylation domain (PS50979, 3-451), ATP-grasp (PS50975, 122-320); Pfam
  Biotin_carb_N, CPSase_L_D2, Biotin_carb_C. PANTHER PTHR45007:SF1. [file:METS5/Msed_0147/Msed_0147-uniprot.txt]
• Gene neighbour: Msed_0148 (BCCP, beta subunit); the two genes appear translationally coupled
  PMID:23530213.
  The carboxyltransferase (gamma) subunit is encoded elsewhere, Msed_1375.

The enzyme

• The carboxylase of the 3HP/4HB cycle was purified from M. sedula. It is one enzyme that acts on both
  acetyl-CoA and propionyl-CoA, a ~560 kDa complex of a 57 kDa biotin carboxylase (alpha), a 57 kDa
  carboxyltransferase (gamma) and an 18.6 kDa biotin carrier (beta), probably (alpha beta gamma)4
  PMID:12581213
  PMID:12581213
  Km 0.06 mM acetyl-CoA, 0.07 mM propionyl-CoA, 0.04 mM ATP, 0.3 mM bicarbonate (abstract).
• Earlier: biotin-dependent ACC and PCC activities in autotrophic M. sedula extracts, and a small
  biotin-carrying protein PMID:9973333.
• Acidianus brierleyi ortholog: alpha4beta4gamma4, bifunctional; ATP-binding residues are in the BC
  subunit PMID:12533469.
• Pathway role: key carboxylating enzyme of the cycle PMID:18079405;
  promiscuous PMID:19684143.
• Gene assignment and induction: PMID:24532060.
• Heterologous function: Msed_0147-0148 + Msed_1375 (E1) expressed in Pyrococcus furiosus gave ACC
  activity (phosphate release from acetyl-CoA, ATP, bicarbonate) and, with E2/E3, 3-HP from CO2
  PMID:23530213.
• ACC is a high flux-control step and is inhibited by malonyl-CoA, succinyl-CoA, ADP and CoA
  PMID:27771364.

• Archaea have no fatty acids, so this ACC does not feed fatty-acid synthesis PMID:9973333.

• Subunit expression: recombinant alpha and gamma subunits made in E. coli were insoluble and inactive;
  active recombinant holoenzyme was obtained only in P. furiosus with the M. sedula biotin protein ligase
  PMID:27315782.

Subunit-level function

The BC subunit performs the first half-reaction: ATP-dependent carboxylation of the biotin on BCCP
(GO:0004075 biotin carboxylase activity, EC 6.3.4.14). The overall acyl-CoA carboxylase activities
(GO:0003989, GO:0004658) belong to the alpha-beta-gamma complex, so the BC subunit contributes_to
them. No individual-subunit assay has been published for the M. sedula enzyme; the half-reaction
assignment rests on the BC domain architecture and on the A. brierleyi homology analysis.

GO annotation decisions

• GO:0004075 biotin carboxylase activity (IEA EC) - ACCEPT, core.
• GO:0005524 ATP binding - KEEP_AS_NON_CORE (substrate binding, part of BC activity).
• GO:0000166 nucleotide binding - MODIFY to ATP binding.
• GO:0046872 metal ion binding - KEEP_AS_NON_CORE (ATP-grasp Mg2+; the ARBA Co2+ cofactor line is unsupported).
• NEW: contributes_to GO:0003989 and GO:0004658; involved_in GO:0015977 carbon fixation.
• CC: GO has no propionyl-CoA carboxylase complex term, and GO:0009317 acetyl-CoA carboxylase complex
  is defined as catalysing "the first step in long-chain fatty acid biosynthesis", which does not fit an
  archaeal enzyme in a CO2-fixation cycle. No CC term is added, and no complex is set in core_functions
  (the generic GO:1902494 catalytic complex would add little). Raised as a suggested question.

Open points

• NCBI esummary was down on 2026-11-01. The uncached PMIDs (12581213, 9973333, 12533469, 27315782)
  were cached with the repo's normal fetch pipeline, using metadata taken from efetch XML.