W6QRN8 · MPADE_PENRF

Function

function

Cytochrome P450 monooxygenase; 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).
MpaDE is an endoplasmic reticulum-bound enzyme that catalyzes the conversion of 5-methylorsellinic acid (5MOA) into the phthalide compound 5,7-dihydroxy-4,6-dimethylphthalide (DHMP) (PubMed:26751579).
MpaDE first catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB), and then acts as a lactone synthase that catalyzes the ring closure to convert DHMB into DHMP (PubMed:26751579).
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

Cofactor

heme (UniProtKB | Rhea| CHEBI:30413 )

Pathway

Secondary metabolite biosynthesis; terpenoid biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site448Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Molecular Functionheme binding
Molecular Functioniron ion binding
Molecular Functionmonooxygenase activity
Molecular Functionoxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
Biological Processmycophenolic acid biosynthetic process
Biological Processterpenoid biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cytochrome P450 monooxygenase mpaDE
  • EC number
  • Alternative names
    • Mycophenolic acid biosynthesis cluster fusion protein DE

Gene names

    • Name
      mpaDE
    • ORF names
      PROQFM164_S05g000557

Organism names

Accessions

  • Primary accession
    W6QRN8

Proteomes

Subcellular Location

Endoplasmic reticulum membrane
; Single-pass membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-6Lumenal
Transmembrane7-29Helical
Topological domain30-852Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Results in dramatic reduction in MPA production and leads to the accumulation of 5-MOA.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004492161-852Cytochrome P450 monooxygenase mpaDE

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Sequence similarities

Belongs to the cytochrome P450 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    852
  • Mass (Da)
    96,209
  • Last updated
    2021-02-10 v2
  • Checksum
    C48E72CDD5344FA2
MDYLIIIRITAVAVVLYLTRYVCCLYLHLQDVPGPLFAKFTNLQRVWWVKSGRAHEYHRRMHAVYGPAVRFGPNMVSISDPRTIPAIYPSRPGFPKSDFYRTQKPYTPNKGAMPAVFNSQDEDLHKRLRSPIAPLYSMTNVVKLESFVDQTLAVLLEQLDGRFLGSNDVPFDLGSWLQYFAFDSMGTLTFSRRYGFLEQGRDMNGILGEIWKFMKRVSVMGQIPWFDEFCNTNPFIALFRSPTGFGVLKVVDKFILQRLAPREKDEVSDEKDMLSQFLNIQASNPDVMPWAPRAWTFSNIMAGSDSTANVMRTIMYNLLVHRDTLSRLQDELLESESSNGLSRTCPSWEKVRDLPYLDACVLEALRLHPPFCLPFERVVPGGGLTVCETYLPAGTIVGISPYMANRDKETFGNDADEWRPERWLGLSHEDRKRLENSLLTFGAGRRTCLGKNIAILEIKKLIPVLLLNYDIQIVNPENYKTENAWFFKQTGLQAVIRKRAKMERGSSNKDKPTLPPVLNIPPSSSTVDVRVIDPGTLLDLRPDLFWQPELPGLRKVTAPTYCFLISVGTRHVLFDLGVRQDWERLPPSVVAMIKSQTTIQNPRNISDILDSDASSLGIRSTDIEAIIWSHAHFDHIGDPSTFPLSTELVVGPGIRDSHWPGFPTNPDAINLNSDIQGRKVREISFERTEKEAIKIGSFDALDYFGDGSFYLLNAAGHSIGHIGALARVTTSPDSFVFMGGDSCHHAGVLRPSKYLPCPSHSRHIPLSSESESVFTLSPVLPSDYDAALKTVDNIKELDAYDNVFLILAHDSTLKGNMDFYPLTINDWKAKGYGKQTKWLFYKDLEDAMEGTK

Sequence caution

The sequence CDM36724.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
HG792019
EMBL· GenBank· DDBJ
CDM36724.1
EMBL· GenBank· DDBJ
Genomic DNA Different initiation

Similar Proteins

Disclaimer

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