W6QL41 · MPAH_PENRF

Function

function

Type I acyl-CoA thioesterase; part of the gene cluster that mediates the biosynthesis of mycophenolic acid (MPA), the first isolated antibiotic natural product in the world obtained from a culture of Penicillium brevicompactum in 1893 (PubMed:26751579).
MpaH acts as a peroxisomal acyl-CoA hydrolase that converts MPA-CoA into the final product MPA (By similarity).
The first step of the pathway is the synthesis of 5-methylorsellinic acid (5MOA) by the cytosolic polyketide synthase mpaC. 5MOA is then converted to the phthalide compound 5,7-dihydroxy-4,6-dimethylphthalide (DHMP) by the endoplasmic reticulum-bound cytochrome P450 monooxygenase mpaDE. MpaDE first catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). MpaDE then acts as a lactone synthase that catalyzes the ring closure to convert DHMB into DHMP. The next step is the prenylation of DHMP by the Golgi apparatus-associated prenyltransferase mpaA to yield farnesyl-DHMP (FDHMP). The ER-bound oxygenase mpaB then mediates the oxidative cleavage the C19-C20 double bond in FDHMP to yield FDHMP-3C via a mycophenolic aldehyde intermediate. The O-methyltransferase mpaG catalyzes the methylation of FDHMP-3C to yield MFDHMP-3C. After the cytosolic methylation of FDHMP-3C, MFDHMP-3C enters into peroxisomes probably via free diffusion due to its low molecular weight. Upon a peroxisomal CoA ligation reaction, catalyzed by a beta-oxidation component enzyme acyl-CoA ligase ACL891, MFDHMP-3C-CoA would then be restricted to peroxisomes for the following beta-oxidation pathway steps. The peroxisomal beta-oxidation machinery than converts MFDHMP-3C-CoA into MPA_CoA, via a beta-oxidation chain-shortening process. Finally mpaH acts as a peroxisomal acyl-CoA hydrolase with high substrate specificity toward MPA-CoA to release the final product MPA (Probable) (PubMed:26751579).

Catalytic activity

Pathway

Secondary metabolite biosynthesis; terpenoid biosynthesis.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site60substrate
Active site139Nucleophile
Binding site140substrate
Active site163
Active site365

GO annotations

AspectTerm
Cellular Componentperoxisomal matrix
Molecular Functionhydrolase activity
Biological Processmycophenolic acid biosynthetic process
Biological Processterpenoid biosynthetic process

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Type I acyl-CoA thioesterase mpaH
  • EC number
  • Alternative names
    • Mycophenolic acid biosynthesis cluster protein H

Gene names

    • Name
      mpaH
    • ORF names
      PROQFM164_S05g000554

Organism names

Accessions

  • Primary accession
    W6QL41

Proteomes

Subcellular Location

Peroxisome matrix
Note: The mpaH' location in peroxisomes is required for the unique cooperation between biosynthetic and beta-oxidation catabolism machineries to produce final MPA.

Keywords

Phenotypes & Variants

Disruption phenotype

Results in dramatic reduction in MPA production.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004492141-433Type I acyl-CoA thioesterase mpaH

Interaction

Subunit

Homodimer.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region58-246Abhydrolase domain

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    433
  • Mass (Da)
    48,633
  • Last updated
    2014-04-16 v1
  • Checksum
    DC67088F2174D14E
MSSEKFTVTEHLVPGSYIREYPGSTVTQEDVLKIHVKQYTPKHEGPVPADAITFIAAHGVGLPKELYEPLWDELLERTNGFHIHGIWVADVASMNQSGIQNEDKLSMDCSWMDHPRDLFLMINHFREQMPRPLVGVGHSFGGNIITNLAYLHPRLFTTLLLIDPLIQLSPPSMGFGTDPPGPINYTLWRNDVWPSREAAIRANRGLIHGWDPRCVDRMAKYFFRDLPTPLYPDVEAVKARFDAAADTTATPVTLATPKYHELIAQIRQNFNARDPTTGRIEIPRATHADMDPLVASIPLYRPEPRSTFRRLGTLRPSCLWIVGGATFLNVDEIHEGVKICGSGIGGSGGVSEGRVKEVILPGLGHLMPFQEIGTVVGPCVAWLQQEMDRFRQMEREWGEERKGKSHLVLEKNWYKVLKPMPSGRGKGGRKEKL

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
HG792019
EMBL· GenBank· DDBJ
CDM36721.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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