MPAB_PENBR
ID MPAB_PENBR Reviewed; 392 AA.
AC F1DBA8;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 19.
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:21398490};
GN Name=mpaB {ECO:0000303|PubMed:21398490};
OS Penicillium brevicompactum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5074;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=IBT 23078;
RX PubMed=21398490; DOI=10.1128/aem.03015-10;
RA Regueira T.B., Kildegaard K.R., Hansen B.G., Mortensen U.H., Hertweck C.,
RA Nielsen J.;
RT "Molecular basis for mycophenolic acid biosynthesis in Penicillium
RT brevicompactum.";
RL Appl. Environ. Microbiol. 77:3035-3043(2011).
RN [2]
RP FUNCTION.
RC STRAIN=IBT23078;
RX PubMed=22544261; DOI=10.1128/aem.07955-11;
RA Hansen B.G., Mnich E., Nielsen K.F., Nielsen J.B., Nielsen M.T.,
RA Mortensen U.H., Larsen T.O., Patil K.R.;
RT "Involvement of a natural fusion of a cytochrome p450 and a hydrolase in
RT mycophenolic acid biosynthesis.";
RL Appl. Environ. Microbiol. 78:4908-4913(2012).
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 (By similarity). MpaB catalyzes the
CC oxidative cleavage the C19-C20 double bond in farnesyl-DHMP (FDHMP) to
CC 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:21398490, PubMed:22544261) (Probable).
CC {ECO:0000250|UniProtKB:A0A0B5LB52, ECO:0000305|PubMed:21398490,
CC ECO:0000305|PubMed:22544261}.
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:21398490}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:A0A0B5LB52}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the mpaB oxygenase family. {ECO:0000305}.
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DR EMBL; HQ731031; ADY00129.1; -; Genomic_DNA.
DR AlphaFoldDB; F1DBA8; -.
DR SMR; F1DBA8; -.
DR UniPathway; UPA00213; -.
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; 2.
DR Pfam; PF09995; MPAB_Lcp_cat; 1.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; Membrane; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..392
FT /note="ER-bound oxygenase mpaB"
FT /id="PRO_0000436571"
FT TOPO_DOM 1..21
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 22..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 42..392
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 352..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 392 AA; 44649 MW; 581A060FBB7C372E CRC64;
MSLPLPPALS ELARALPYSR TQWLPIFVGF LIGYPILIRA LRYKRHGEMK KKFYFPTRES
MAEMTDEEAF LIQKEMAQLE FPFMFLTSGQ FALFRTYGIP TISHLLTKTG QFSKPETSFK
RYTDTAALIG EMVENSPTSQ RAFISVARTR FLHSGYQASG KILDADLLYT LALFAVQPVR
FIENFEWRTL SDLELCAIGT FWKSLGDALG ISSEILPSGK TGFKDGIQWL EEVDVWSQDY
EAKYMVPDPK NRESADQATA MLISNRYEAP TPGWSMVFST LLAIRKLILR YLSPPRPAAL
AVSNIAQKPD KDDRYHRMSW DALPFYIRPT FWNRWGPMAW ISWLMGHPVP GDLGQKKGPQ
GDPGNDEGIK DLKDGEMSLP LVWSKYHATT ND
