MPAB2_PENBR
ID MPAB2_PENBR Reviewed; 423 AA.
AC A0A0B5LB52;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=ER-bound oxygenase mpaB' {ECO:0000303|PubMed:25630520};
DE EC=1.-.-.- {ECO:0000269|PubMed:31209052};
DE AltName: Full=Mycophenolic acid biosynthesis cluster protein B' {ECO:0000303|PubMed:25630520};
GN Name=mpaB' {ECO:0000303|PubMed:25630520};
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].
RC STRAIN=NRRL864;
RX PubMed=25630520; DOI=10.1002/cbic.201402600;
RA Zhang W., Cao S., Qiu L., Qi F., Li Z., Yang Y., Huang S., Bai F., Liu C.,
RA Wan X., Li S.;
RT "Functional characterization of MpaG', the O-methyltransferase involved in
RT the biosynthesis of mycophenolic acid.";
RL ChemBioChem 16:565-569(2015).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY,
RP AND PATHWAY.
RX PubMed=31209052; DOI=10.1073/pnas.1821932116;
RA Zhang W., Du L., Qu Z., Zhang X., Li F., Li Z., Qi F., Wang X., Jiang Y.,
RA Men P., Sun J., Cao S., Geng C., Qi F., Wan X., Liu C., Li S.;
RT "Compartmentalized biosynthesis of mycophenolic acid.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:13305-13310(2019).
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:31209052). 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
CC (PubMed:31209052). 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:31209052) (Probable). {ECO:0000269|PubMed:31209052,
CC ECO:0000305|PubMed:31209052}.
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:0000269|PubMed:31209052};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66689;
CC Evidence={ECO:0000269|PubMed:31209052};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31209052}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:31209052}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Leads to a dramatically decreased production of
CC MPA and accumulates significant amounts of farnesyl-DHMP (FDHMP) in
CC mycelia. {ECO:0000269|PubMed:31209052}.
CC -!- SIMILARITY: Belongs to the mpaB oxygenase family. {ECO:0000305}.
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DR EMBL; KM595305; AJG44380.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0B5LB52; -.
DR SMR; A0A0B5LB52; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:GO_Central.
DR GO; GO:0140722; P:mycophenolic acid biosynthetic process; IDA: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 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; Oxidoreductase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..423
FT /note="ER-bound oxygenase mpaB'"
FT /id="PRO_0000451890"
FT TOPO_DOM 1..22
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:31209052"
FT TRANSMEM 23..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 42..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:31209052"
SQ SEQUENCE 423 AA; 48569 MW; 3980B0340DE08F5E CRC64;
MSLSLPPALS ELARALPYSR TQWLPILVGF LIGYPLLIKA LRYKRLGEMK KKFYFPTRES
MAEMTDEEAF LIQKEMAQLE FPFMFLTSGQ FALFRTYGIP TISHLLTKTG QFSKPETSFK
RYTDTAALIG EMVENSPTSQ RAFISVARTR FLHSGYQASG KILDADLLYT LALFAVQPVR
FIENFEWRTL SDLELCAIGT FWKSLGDALG ISSEILPSGK TGFKDGIQWL EEVDVWSQDY
EAKYMVPDPK NRESADQATA VLLYNLPKIL HPIGLQFTSY MMDDRLRKAM LYEAPSPGWS
AVFSSLLATR KFVLRYLSPP RPAALAVSNI AQKPDKDDRY HRMSWDALPF YIRPTFWNRW
GPMAWISWLM AHPVPGDHGQ KYYPQGYHIQ DIGPKYFEGK GHKEIQEMMK ELKISRTGKC
PFH
