MPAA_PENRF
ID MPAA_PENRF Reviewed; 325 AA.
AC W6QIT8;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Polyprenyl transferase mpaA {ECO:0000303|PubMed:26751579};
DE EC=2.5.1.- {ECO:0000305|PubMed:26751579};
DE AltName: Full=Mycophenolic acid biosynthesis cluster protein A {ECO:0000303|PubMed:26751579};
GN Name=mpaA {ECO:0000303|PubMed:26751579}; ORFNames=PROQFM164_S05g000561;
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: 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:26751579). 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:26751579). 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:26751579) (Probable).
CC {ECO:0000269|PubMed:26751579, ECO:0000305|PubMed:26751579}.
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:0000305|PubMed:26751579};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66677;
CC Evidence={ECO:0000305|PubMed:26751579};
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:26751579}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:A0A0B5L778}; 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}.
CC -!- DISRUPTION PHENOTYPE: Results in dramatic reduction in MPA production
CC and leads to the accumulation of DHMP. {ECO:0000269|PubMed:26751579}.
CC -!- SIMILARITY: Belongs to the UbiA prenyltransferase family.
CC {ECO:0000305}.
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DR EMBL; HG792019; CDM36728.1; -; Genomic_DNA.
DR AlphaFoldDB; W6QIT8; -.
DR SMR; W6QIT8; -.
DR STRING; 1365484.W6QIT8; -.
DR EnsemblFungi; CDM36728; CDM36728; PROQFM164_S05g000561.
DR OrthoDB; 1343847at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000030686; Unassembled WGS sequence.
DR GO; GO:0005794; C:Golgi apparatus; ISS: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; IMP:GO_Central.
DR GO; GO:0140722; P:mycophenolic acid biosynthetic process; IMP: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 3: Inferred from homology;
KW Glycoprotein; Golgi apparatus; Membrane; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..325
FT /note="Polyprenyl transferase mpaA"
FT /id="PRO_0000449212"
FT TRANSMEM 27..47
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 325 AA; 36985 MW; 8A7E743503E3CC30 CRC64;
MVGSMENPGS WGLACLLIST SRFNRYMPYY TMMAAVWSTL IAGALKLQED PASLSVEYIL
FKAGLCFVHC LLLCGAGNTW NDLIDRDIDA RVERTKMRPL ASGKVSTVEA LVWMVGQYFL
SVKMLDLILD NRSIWGLMLP LTASIMLYPY LKRPVFSRVF IYPQYILGLA VAYPSITGWA
SINGQEQSMS EIFTHCTPIC LLIFFWCLYF NTAYSHQDSV DDRKMNINSA YVVAGQRIRL
FLAFLGALPL AVIPYVVLKI NSPWLWFSWM AVWTVSIVMQ IVRFDSKKLE SGGRIHWDNF
LLGLWTTVAC IVEVGLQKVE FWNLI
