Protein: O-methyltransferase mpaG' (EC 2.1.1.-) (Mycophenolic acid biosynthesis cluster protein G') (A0A0B5L781)
Organism: Penicillium brevicompactum
Function: O-methyltransferase; part of the gene cluster that mediates the biosynthesis of mycophenolic acid (MPA), the first isolated antibiotic natural product in the world obtained from a culture of Penicillium brevicompactum in 1893. MpaG' methylates farnesyl-DHMP-3C (FDHMP-3C) to yield MFDHMP-3C. The first step of the pathway is the synthesis of 5-methylorsellinic acid (5MOA) by the cytosolic polyketide synthase mpaC. 5MOA is then converted to the phthalide compound 5,7-dihydroxy-4,6-dimethylphthalide (DHMP) by the endoplasmic reticulum-bound cytochrome P450 monooxygenase mpaDE. MpaDE first catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). MpaDE then acts as a lactone synthase that catalyzes the ring closure to convert DHMB into DHMP. The next step is the prenylation of DHMP by the Golgi apparatus-associated prenyltransferase mpaA to yield farnesyl-DHMP (FDHMP). The ER-bound oxygenase mpaB then mediates the oxidative cleavage the C19-C20 double bond in FDHMP to yield FDHMP-3C via a mycophenolic aldehyde intermediate. The O-methyltransferase mpaG catalyzes the methylation of FDHMP-3C to yield MFDHMP-3C. After the cytosolic methylation of FDHMP-3C, MFDHMP-3C enters into peroxisomes probably via free diffusion due to its low molecular weight. Upon a peroxisomal CoA ligation reaction, catalyzed by a beta-oxidation component enzyme acyl-CoA ligase ACL891, MFDHMP-3C-CoA would then be restricted to peroxisomes for the following beta-oxidation pathway steps. The peroxisomal beta-oxidation machinery than converts MFDHMP-3C-CoA into MPA_CoA, via a beta-oxidation chain-shortening process. Finally mpaH acts as a peroxisomal acyl-CoA hydrolase with high substrate specificity toward MPA-CoA to release the final product MPA (Probable).
Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:31209052}.
Sequence: MSAASPASIIQELASAAKQYENNESGAREALIAQSRALIASLEVPSEFIQHTFWSQPALSAIVRLATDVNLFQYLKDAQEEGLNAEALASKTGMDVSLFARLARHLVAMNVITSRNGVFYGTALSNGLAAENYQQSIRFCHDVSRPSFGAFPSFFKGNGYKTPALGTTDGPFQSAHKVDISFPQWLVGNPPYLQYFNSYMSAYRAGKPNWCDNGFYPVADRLLNGFDASVSDVLLVDVGGGRGHDIATFGSQFSPLPGRLVLQDREQVINSIPADESRQFEATTHDIFTTQPVKHARAYYMHSVPHGFGDEDAVKIMANLVPALAKGYSRVLLNEIVVDEERPVMSATNMDLIMLAHMGAKERTEADWRSILTRAGLKVVNIYSYPGVAESLIEAELA
InterPro domains: - IPR036390: Winged helix DNA-binding domain superfamily (homologous_superfamily) [51-129]
- IPR029063: S-adenosyl-L-methionine-dependent methyltransferase superfamily (homologous_superfamily) [138-396]
- IPR001077: O-methyltransferase, C-terminal domain (domain) [220-377]
- IPR016461: O-methyltransferase-like (family) [35-397]
- IPR036388: Winged helix-like DNA-binding domain superfamily (homologous_superfamily) [51-142]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0016741 (transferase activity, transferring one-carbon groups), GO:0008168 (methyltransferase activity), GO:0008171 (O-methyltransferase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0043386 (mycotoxin biosynthetic process), GO:1901336 (lactone biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)