Msed_1456 (A4YGR1, HPCAS_METS5) notes

Automated deep research was unavailable for this gene. These notes come from
manual literature research (NCBI E-utilities searches, the full-text cached
publications listed below, and the UniProt record).

Identity

• Msed_1456 is 3-hydroxypropionyl-CoA synthetase (HPCS), EC 6.2.1.36, 661 aa,
  an AMP-forming acyl-CoA synthetase (ANL superfamily; UniProt "Belongs to the
  ATP-dependent AMP-binding enzyme family"). InterPro places it in the
  acetyl-CoA ligase family (IPR011904, TIGR02188 Ac_CoA_lig_AcsA) and PANTHER
  PTHR24095 (acetyl-coenzyme A synthetase), which is why acetyl-CoA synthetase
  terms are propagated to it.
• Identified by purification of the native enzyme from autotrophically grown
  M. sedula and an internal peptide PMID:18165310.

Activity and substrate specificity

• Reaction PMID:18165310.
• Kinetics PMID:18165310.
• Specificity: 3HP and propionate are equivalent; acrylate ~10-fold lower
  kcat/Km; acetate and butyrate only weakly used, attributed to low affinity
  PMID:18165310
  PMID:18165310.
• Independent comparison by Hawkins et al. PMID:23258541.
• The M. sedula acetate-activating enzyme is a different paralog, Msed_1353
  PMID:23258541.
  This, plus the weak acetate affinity of Msed_1456, makes the acetyl-CoA
  synthetase activity and acetyl-CoA biosynthesis IEA rows family-level
  over-annotation (ARCHAEA pattern 1-like: a substrate-diverged ANL member
  inheriting the family-founder name).
• Homotetramer of 78 kDa subunits PMID:18165310.
• Induced under autotrophy PMID:18165310.

Pathway

• Activates 3-hydroxypropionate, the first committed step of the reductive
  conversion 3HP -> 3HP-CoA -> acryloyl-CoA -> propionyl-CoA, in the first half of
  the 3HP/4HB cycle. Acetyl-CoA is regenerated in the second half via
  4-hydroxybutyrate PMID:18079405.
  Msed_1456 itself does not produce acetyl-CoA.
• GO:0043427 "carbon fixation by 3-hydroxypropionate cycle" (OLS, checked
  2026-10-31): "An autotrophic carbon dioxide fixation pathway by which two
  molecules of carbon dioxide are fixed to form glyoxylate ... Malyl-CoA is
  thought to be cleaved to acetyl-CoA, the starting molecule, and glyoxylate".
  This is the Chloroflexus pathway; M. sedula lacks malyl-CoA lyase
  PMID:18165310.
  No GO term for the 3HP/4HB cycle exists (OLS search). Following the
  Msed_0709 review, the IDA/IEA GO:0043427 rows are MODIFIED to the NTR
  "carbon fixation by 3-hydroxypropionate/4-hydroxybutyrate cycle" plus
  GO:0015977 carbon fixation. The activity evidence of the IDA is sound.
• Recombinant M. sedula HPCS is insoluble alone in E. coli; it is
  soluble only when co-expressed with 3HP-CoA dehydratase Msed_2001, and the
  two interact in yeast two-hybrid
  PMID:27771364
  PMID:27771364.
  Possible substrate channelling; not annotated (Y2H only).

Other

• PMID:27722922 and PMID:27300329 (engineering of part of the cycle in
  E. coli / in vitro) were cached but are not used; 27722922 is abstract-only.