MPAB_PENRF
ID MPAB_PENRF Reviewed; 298 AA.
AC W6R4H8;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=ER-bound oxygenase mpaB {ECO:0000250|UniProtKB:A0A0B5LB52};
DE EC=1.-.-.- {ECO:0000250|UniProtKB:A0A0B5LB52};
DE AltName: Full=Mycophenolic acid biosynthesis cluster protein B {ECO:0000303|PubMed:26751579};
GN Name=mpaB {ECO:0000303|PubMed:26751579}; ORFNames=PROQFM164_S05g000560;
OS Penicillium roqueforti (strain FM164).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=1365484;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FM164;
RX PubMed=24407037; DOI=10.1038/ncomms3876;
RA Cheeseman K., Ropars J., Renault P., Dupont J., Gouzy J., Branca A.,
RA Abraham A.L., Ceppi M., Conseiller E., Debuchy R., Malagnac F., Goarin A.,
RA Silar P., Lacoste S., Sallet E., Bensimon A., Giraud T., Brygoo Y.;
RT "Multiple recent horizontal transfers of a large genomic region in cheese
RT making fungi.";
RL Nat. Commun. 5:2876-2876(2014).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=26751579; DOI=10.1371/journal.pone.0147047;
RA Del-Cid A., Gil-Duran C., Vaca I., Rojas-Aedo J.F., Garcia-Rico R.O.,
RA Levican G., Chavez R.;
RT "Identification and functional analysis of the mycophenolic acid gene
RT cluster of Penicillium roqueforti.";
RL PLoS ONE 11:E0147047-E0147047(2016).
CC -!- FUNCTION: ER-bound oxygenase; part of the gene cluster that mediates
CC the biosynthesis of mycophenolic acid (MPA), the first isolated
CC antibiotic natural product in the world obtained from a culture of
CC Penicillium brevicompactum in 1893 (PubMed:26751579). MpaB catalyzes
CC the oxidative cleavage the C19-C20 double bond in farnesyl-DHMP (FDHMP)
CC to yield FDHMP-3C via a mycophenolic aldehyde intermediate (By
CC similarity). The first step of the pathway is the synthesis of 5-
CC methylorsellinic acid (5MOA) by the cytosolic polyketide synthase mpaC.
CC 5MOA is then converted to the phthalide compound 5,7-dihydroxy-4,6-
CC dimethylphthalide (DHMP) by the endoplasmic reticulum-bound cytochrome
CC P450 monooxygenase mpaDE. MpaDE first catalyzes hydroxylation of 5-MOA
CC to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). MpaDE
CC then acts as a lactone synthase that catalyzes the ring closure to
CC convert DHMB into DHMP. The next step is the prenylation of DHMP by the
CC Golgi apparatus-associated prenyltransferase mpaA to yield farnesyl-
CC DHMP (FDHMP). The ER-bound oxygenase mpaB then mediates the oxidative
CC cleavage the C19-C20 double bond in FDHMP to yield FDHMP-3C via a
CC mycophenolic aldehyde intermediate. The O-methyltransferase mpaG
CC catalyzes the methylation of FDHMP-3C to yield MFDHMP-3C. After the
CC cytosolic methylation of FDHMP-3C, MFDHMP-3C enters into peroxisomes
CC probably via free diffusion due to its low molecular weight. Upon a
CC peroxisomal CoA ligation reaction, catalyzed by a beta-oxidation
CC component enzyme acyl-CoA ligase ACL891, MFDHMP-3C-CoA would then be
CC restricted to peroxisomes for the following beta-oxidation pathway
CC steps. The peroxisomal beta-oxidation machinery than converts MFDHMP-
CC 3C-CoA into MPA_CoA, via a beta-oxidation chain-shortening process.
CC Finally mpaH acts as a peroxisomal acyl-CoA hydrolase with high
CC substrate specificity toward MPA-CoA to release the final product MPA
CC (PubMed:26751579) (Probable). {ECO:0000250|UniProtKB:A0A0B5LB52,
CC ECO:0000269|PubMed:26751579, ECO:0000305|PubMed:26751579}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-farnesyl-3,5-dihydroxy-6-methylphthalide + AH2 + 2 O2 =
CC (4E,8E)-10-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-
CC yl)-4,8-dimethyldeca-4,8-dienoate + A + acetone + H(+) + H2O;
CC Xref=Rhea:RHEA:66688, ChEBI:CHEBI:13193, ChEBI:CHEBI:15347,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:167386, ChEBI:CHEBI:167389;
CC Evidence={ECO:0000250|UniProtKB:A0A0B5LB52};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66689;
CC Evidence={ECO:0000250|UniProtKB:A0A0B5LB52};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:26751579}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:A0A0B5LB52}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Results in dramatic reduction in MPA production.
CC {ECO:0000269|PubMed:26751579}.
CC -!- SIMILARITY: Belongs to the mpaB oxygenase family. {ECO:0000305}.
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DR EMBL; HG792019; CDM36727.1; -; Genomic_DNA.
DR AlphaFoldDB; W6R4H8; -.
DR SMR; W6R4H8; -.
DR EnsemblFungi; CDM36727; CDM36727; PROQFM164_S05g000560.
DR OrthoDB; 1136963at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000030686; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:GO_Central.
DR GO; GO:0140722; P:mycophenolic acid biosynthetic process; ISS:GO_Central.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR046366; MPAB.
DR InterPro; IPR018713; MPAB/Lcp_cat_dom.
DR PANTHER; PTHR36124; PTHR36124; 1.
DR Pfam; PF09995; MPAB_Lcp_cat; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Membrane; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..298
FT /note="ER-bound oxygenase mpaB"
FT /id="PRO_0000449213"
FT TOPO_DOM 1..24
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..298
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
SQ SEQUENCE 298 AA; 34083 MW; 7F57D956BF6A6133 CRC64;
MDKGTSFFTT PSFSATTRAI FNTMPQWFSF AVGLLIAYPL LINSLRYRRL KQLQKKFYFP
TRESMAKMTD EEAFQIQKET AQLEFPFMFV KAGQFALFRT YGIPTISHLL IKTGQFSKPE
TSFKRYTDTA ALIGEMVENS PTSQRAFLSV ARTRFLHSGY QASGKILDTD LLYTLALFAV
QPVNFIAAFE WRPLSDLERC AIGTFWKSLG DALGISSDIL PSGKTGFRDG IHWLEEVDTW
SQEYEVKYMV PDAQNRESAD QATAVLLYNL PKVFHPVGLQ FTSFMMDDRL RKAMLYVE
