MPAA2_PENBR
ID MPAA2_PENBR Reviewed; 331 AA.
AC A0A0B5L778;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Polyprenyl transferase mpaA' {ECO:0000303|PubMed:25630520};
DE EC=2.5.1.- {ECO:0000269|PubMed:31209052};
DE AltName: Full=Mycophenolic acid biosynthesis cluster protein A' {ECO:0000303|PubMed:25630520};
GN Name=mpaA' {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, CATALYTIC ACTIVITY, 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: Polyprenyl transferase; part of the gene cluster that
CC mediates the biosynthesis of mycophenolic acid (MPA), the first
CC isolated antibiotic natural product in the world obtained from a
CC culture of Penicillium brevicompactum in 1893 (PubMed:31209052). MpaA'
CC is a Golgi apparatus-associated enzyme that catalyzes the prenylation
CC of 5,7-dihydroxy-4,6-dimethylphthalide (DHMP) to yield farnesyl-DHMP
CC (FDHMP) (PubMed:31209052). The first step of the pathway is the
CC synthesis of 5-methylorsellinic acid (5MOA) by the cytosolic polyketide
CC synthase mpaC. 5MOA is then converted to the phthalide compound 5,7-
CC dihydroxy-4,6-dimethylphthalide (DHMP) by the endoplasmic reticulum-
CC bound cytochrome P450 monooxygenase mpaDE. MpaDE first catalyzes
CC hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-
CC methylbenzoic acid (DHMB). MpaDE then acts as a lactone synthase that
CC catalyzes the ring closure to convert DHMB into DHMP. The next step is
CC the prenylation of DHMP by the Golgi apparatus-associated
CC prenyltransferase mpaA to yield farnesyl-DHMP (FDHMP). The ER-bound
CC oxygenase mpaB then mediates the oxidative cleavage the C19-C20 double
CC bond in FDHMP to yield FDHMP-3C via a mycophenolic aldehyde
CC intermediate. The O-methyltransferase mpaG catalyzes the methylation of
CC FDHMP-3C to yield MFDHMP-3C. After the cytosolic methylation of FDHMP-
CC 3C, MFDHMP-3C enters into peroxisomes probably via free diffusion due
CC to its low molecular weight. Upon a peroxisomal CoA ligation reaction,
CC catalyzed by a beta-oxidation component enzyme acyl-CoA ligase ACL891,
CC MFDHMP-3C-CoA would then be restricted to peroxisomes for the following
CC beta-oxidation pathway steps. The peroxisomal beta-oxidation machinery
CC than converts MFDHMP-3C-CoA into MPA_CoA, via a beta-oxidation chain-
CC shortening process. Finally mpaH acts as a peroxisomal acyl-CoA
CC hydrolase with high substrate specificity toward MPA-CoA to release the
CC final product MPA (PubMed:31209052) (Probable).
CC {ECO:0000269|PubMed:31209052, ECO:0000305|PubMed:31209052}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + 5,7-dihydroxy-4-methylphthalide
CC = 4-farnesyl-3,5-dihydroxy-6-methylphthalide + diphosphate;
CC Xref=Rhea:RHEA:66676, ChEBI:CHEBI:33019, ChEBI:CHEBI:68194,
CC ChEBI:CHEBI:167386, ChEBI:CHEBI:175763;
CC Evidence={ECO:0000269|PubMed:31209052};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66677;
CC Evidence={ECO:0000269|PubMed:31209052};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P32378};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31209052}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:31209052}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Membrane association is functionally relevant
CC because mpaA must ostensibly interact with its membrane-embedded
CC substrate FPP. {ECO:0000305|PubMed:31209052}.
CC -!- SIMILARITY: Belongs to the UbiA prenyltransferase family.
CC {ECO:0000305}.
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DR EMBL; KM595305; AJG44379.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0B5L778; -.
DR SMR; A0A0B5L778; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0005794; C:Golgi apparatus; IDA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004659; F:prenyltransferase 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 CDD; cd13959; PT_UbiA_COQ2; 1.
DR Gene3D; 1.10.357.140; -; 1.
DR InterPro; IPR039653; Prenyltransferase.
DR InterPro; IPR000537; UbiA_prenyltransferase.
DR InterPro; IPR030470; UbiA_prenylTrfase_CS.
DR InterPro; IPR044878; UbiA_sf.
DR PANTHER; PTHR11048; PTHR11048; 1.
DR Pfam; PF01040; UbiA; 1.
DR PROSITE; PS00943; UBIA; 1.
PE 1: Evidence at protein level;
KW Golgi apparatus; Magnesium; Membrane; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..331
FT /note="Polyprenyl transferase mpaA'"
FT /id="PRO_0000451889"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 331 AA; 37738 MW; 301E9EC2292C969F CRC64;
MTNAVEDSGP RDLLFLLIST SRFNRYMPYY TMMAAVWATF IAGALKLQQD PESLSIEFIL
YKAGLCFVHC LLLCGAGNTW NDLVDRDIDA RVARTKMRPL ASGKVTLTEA LLWMTGQYFL
SVKMLDLILD GRNIWTLMLP LTASIMLYPY LKRPIFSKVF VYPQYILGLA IGYPAITGWA
SITGSEEPLG DIIKHCIPIC LLVFFWCVYF NTAYSHQDSV DDRKMNINSA YVIAGQRIRL
FLAFLSVLPL LTIPYIISTI NSPWLWVSWM ATWTVSIVMQ IAQFDSQKLE SGGRIHWDNF
LLGLWTIVAC MVEVGLQKVE FWKNVEGYIK L
