MPAG2_PENBR
ID MPAG2_PENBR Reviewed; 398 AA.
AC A0A0B5L781;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=O-methyltransferase mpaG' {ECO:0000303|PubMed:25630520};
DE EC=2.1.1.- {ECO:0000269|PubMed:25630520, ECO:0000269|PubMed:31209052};
DE AltName: Full=Mycophenolic acid biosynthesis cluster protein G' {ECO:0000303|PubMed:25630520};
GN Name=mpaG' {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], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
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, AND CATALYTIC ACTIVITY.
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: O-methyltransferase; 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:25630520, PubMed:31209052).
CC MpaC' methylates farnesyl-DHMP-3C (FDHMP-3C) to yield MFDHMP-3C
CC (PubMed:25630520, PubMed:31209052). The first step of the pathway is
CC the synthesis of 5-methylorsellinic acid (5MOA) by the cytosolic
CC polyketide synthase mpaC. 5MOA is then converted to the phthalide
CC compound 5,7-dihydroxy-4,6-dimethylphthalide (DHMP) by the endoplasmic
CC reticulum-bound cytochrome P450 monooxygenase mpaDE. MpaDE first
CC catalyzes 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:25630520, ECO:0000269|PubMed:31209052,
CC ECO:0000305|PubMed:31209052}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4E,8E)-10-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-
CC benzofuran-5-yl)-4,8-dimethyldeca-4,8-dienoate + S-adenosyl-L-
CC methionine = (4E,8E)-10-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-
CC dihydro-2-benzofuran-5-yl)-4,8-dimethyldeca-4,8-dienoate + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:66696, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:167389,
CC ChEBI:CHEBI:167390; Evidence={ECO:0000269|PubMed:25630520,
CC ECO:0000269|PubMed:31209052};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66697;
CC Evidence={ECO:0000269|PubMed:25630520, ECO:0000269|PubMed:31209052};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31209052}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:31209052}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KM595305; AJG44384.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0B5L781; -.
DR SMR; A0A0B5L781; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0005829; C:cytosol; IDA:GO_Central.
DR GO; GO:0008168; F:methyltransferase activity; IDA:GO_Central.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0140722; P:mycophenolic acid biosynthetic process; IDA:GO_Central.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR PIRSF; PIRSF005739; O-mtase; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..398
FT /note="O-methyltransferase mpaG'"
FT /id="PRO_0000451894"
FT ACT_SITE 306
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT ACT_SITE 335
FT /evidence="ECO:0000250|UniProtKB:F1DBB3"
FT ACT_SITE 362
FT /evidence="ECO:0000250|UniProtKB:F1DBB3"
FT BINDING 264
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ SEQUENCE 398 AA; 43553 MW; C633552CD25B4A57 CRC64;
MSAASPASII QELASAAKQY ENNESGAREA LIAQSRALIA SLEVPSEFIQ HTFWSQPALS
AIVRLATDVN LFQYLKDAQE EGLNAEALAS KTGMDVSLFA RLARHLVAMN VITSRNGVFY
GTALSNGLAA ENYQQSIRFC HDVSRPSFGA FPSFFKGNGY KTPALGTTDG PFQSAHKVDI
SFPQWLVGNP PYLQYFNSYM SAYRAGKPNW CDNGFYPVAD RLLNGFDASV SDVLLVDVGG
GRGHDIATFG SQFSPLPGRL VLQDREQVIN SIPADESRQF EATTHDIFTT QPVKHARAYY
MHSVPHGFGD EDAVKIMANL VPALAKGYSR VLLNEIVVDE ERPVMSATNM DLIMLAHMGA
KERTEADWRS ILTRAGLKVV NIYSYPGVAE SLIEAELA
