A0A348HAY5 · PHIJ_FUNX7

Function

function

Alkylcitrate synthase; part of the gene cluster that mediates the biosynthesis of the antihypercholesterolemic agents phomoidrides which are dimeric anhydrides (PubMed:26558485).
Within the pathway, the alkylcitrate synthase (ACS) phiJ and the alkylcitrate dehydratase (ACDH) phiI produce the decarboxylated monomeric anhydrides by coupling the C12-fatty acyl product from phiA with oxalacetic acid (PubMed:26558485).
The pathway begins with the highly reducing polyketide synthase phiA that catalyzes the formation of a C12-fatty acyl-ACP, starting from one acetate and 5 malonate units. The hydrolase phiM is involved in the release of the C12-fatty acyl chain from phiA. The alkylcitrate synthase (ACS) phiJ and the alkylcitrate dehydratase (ACDH) phiI then give rise to decarboxylated monomeric anhydrides by coupling the C12-fatty acyl chain with oxalacetic acid. The cyclase phiC is responsible for the dimerization of the monomeric anhydrides which leads to the production of prephomoidride that contains the characteristic bicyclo[4.3.1]deca-1,6-diene system of phomoidrides. Iterative oxidation catalyzed by the alpha-ketoglutarate-dependent dioxygenase phiK produced then phomoidride A. Finally, the methyltransferase phiE converts phomoidride A to phomoidride B via an acetalization reaction. The phosphatidylethanolamine-binding protein phiB and phiN are not essential for dimerization and their functions have still to be determined (Probable)

Catalytic activity

Biotechnology

Phomoidrides A and B (also known as CP-225,917 and CP-263,114) are potent inhibitors of Ras farnesyltransferase and squalene synthase (PubMed:9066758).
CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 uM and 20 uoM, respectively (PubMed:9066758).
CP-225,917 inhibits squalene synthase with an IC50 value of 43 uM and CP-263,114 with an IC50 of 160 uM (PubMed:9066758).

Pathway

Secondary metabolite biosynthesis.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site328
Active site384

GO annotations

AspectTerm
Cellular Componentmitochondrial matrix
Molecular Functioncitrate (Si)-synthase activity
Biological Processcarbohydrate metabolic process
Biological Processtricarboxylic acid cycle

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Alkylcitrate synthase phiJ
  • EC number
  • Short names
    ACS
  • Alternative names
    • Phomoidride biosynthesis cluster protein I

Gene names

    • Name
      phiJ

Organism names

Accessions

  • Primary accession
    A0A348HAY5

Subcellular Location

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004589461-457Alkylcitrate synthase phiJ

Expression

Induction

expression is induced under low pH conditions.

Family & Domains

Sequence similarities

Belongs to the citrate synthase family.

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    457
  • Mass (Da)
    51,194
  • Last updated
    2018-11-07 v1
  • Checksum
    EF52E00506D400FB
MALSSQAQGKLFVRDSRTSREYEIPISNNTINAADFQKINLPTKGKSLTKALGLQLYDPGMQNTAIKKTEIIGRDPSTGLPLLRGVTSQELWKRRCDFEELFSLMVFGNYPTIVEREALRYQFAEYMKEVPKVVGSVIRKFPPSSPPLPMITAGLSAYLSSDPDFIPAIHGGNIYHRNPRAADEAAIKTAAVYAVVIGLISCHKKGINFVPADTDDTFLENLFRMCGLVDPATRRPDPHVLAVFRKGLVLNCDNGMTQSNLVLCATASSLCDPISCLISAISAAYGPLHYGAQEAGYRTLSEIGSADRVPHFLEQVKRRERRLFGYGHRTFATEDPRLNAVKGWLQELDFDSKREPLMKIAEEIDRLAAQDDYFTSRGLRANADFYTLFVFRAYGFDWDMIGAANFCMRIIGFMAHWREAMEQEIKIFRARDYYVGPSKKDPNRESSGTGILAQARL

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
LC086931
EMBL· GenBank· DDBJ
BBG28507.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

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