PRHM_PENBI
ID PRHM_PENBI Reviewed; 279 AA.
AC A0A1E1FFN5;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Methyltransferase prhM {ECO:0000303|PubMed:27602587};
DE EC=2.1.3.- {ECO:0000305|PubMed:27602587};
DE AltName: Full=Paraherquonin biosynthesis cluster protein M {ECO:0000303|PubMed:27602587};
GN Name=prhM {ECO:0000303|PubMed:27602587};
OS Penicillium brasilianum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=104259;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=ATCC 22354 / NBRC 6234 / CBS 338.59 / FRR 3454 / IMI 68220;
RX PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA Zhang H., Hayashi F., Abe I.;
RT "Discovery of key dioxygenases that diverged the paraherquonin and
RT acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL J. Am. Chem. Soc. 138:12671-12677(2016).
RN [2]
RP FUNCTION.
RX PubMed=28759016; DOI=10.1038/nchembio.2443;
RA Mori T., Iwabuchi T., Hoshino S., Wang H., Matsuda Y., Abe I.;
RT "Molecular basis for the unusual ring reconstruction in fungal
RT meroterpenoid biogenesis.";
RL Nat. Chem. Biol. 13:1066-1073(2017).
RN [3]
RP FUNCTION.
RX PubMed=29317628; DOI=10.1038/s41467-017-02371-w;
RA Nakashima Y., Mori T., Nakamura H., Awakawa T., Hoshino S., Senda M.,
RA Senda T., Abe I.;
RT "Structure function and engineering of multifunctional non-heme iron
RT dependent oxygenases in fungal meroterpenoid biosynthesis.";
RL Nat. Commun. 9:104-104(2018).
CC -!- FUNCTION: Methyltransferase; part of the gene cluster that mediates the
CC biosynthesis of paraherquonin, a meroterpenoid with a unique, highly
CC congested hexacyclic molecular architecture (PubMed:27602587). The
CC first step of the pathway is the synthesis of 3,5-dimethylorsellinic
CC acid (DMOA) by the polyketide synthase prhL (By similarity). Synthesis
CC of DMOA is followed by farnesylation by the prenyltransferase prhE,
CC methylesterification by the methyl-transferase prhM, epoxidation of the
CC prenyl chain by the flavin-dependent monooxygenase prhF, and
CC cyclization of the farnesyl moiety by the terpene cyclase prhH, to
CC yield the tetracyclic intermediate, protoaustinoid A (By similarity).
CC The short chain dehydrogenase prhI then oxidizes the C-3 alcohol group
CC of the terpene cyclase product to transform protoaustinoid A into
CC protoaustinoid B (PubMed:27602587). The FAD-binding monooxygenase prhJ
CC catalyzes the oxidation of protoaustinoid B into preaustinoid A which
CC is further oxidized into preaustinoid A1 by FAD-binding monooxygenase
CC phrK (PubMed:27602587). Finally, prhA leads to berkeleydione via the
CC berkeleyone B intermediate (PubMed:27602587, PubMed:29317628). PrhA is
CC a multifunctional dioxygenase that first desaturates at C5-C6 to form
CC berkeleyone B, followed by rearrangement of the A/B-ring to form the
CC cycloheptadiene moiety in berkeleydione (PubMed:27602587,
CC PubMed:29317628). Berkeleydione serves as the key intermediate for the
CC biosynthesis of paraherquonin as well as many other meroterpenoids
CC (Probable). The cytochrome P450 monooxygenases prhB, prhD, and prhN, as
CC well as the isomerase prhC, are probably involved in the late stage of
CC paraherquonin biosynthesis, after the production of berkeleydione
CC (Probable). Especially prhC might be a multifunctional enzyme that
CC catalyzes the D-ring expansion via intramolecular methoxy
CC rearrangement, as well as the hydrolysis of the expanded D-ring
CC (Probable). {ECO:0000250|UniProtKB:Q5ATJ7, ECO:0000269|PubMed:27602587,
CC ECO:0000269|PubMed:29317628, ECO:0000305|PubMed:27602587,
CC ECO:0000305|PubMed:28759016, ECO:0000305|PubMed:29317628}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:27602587}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. {ECO:0000305}.
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DR EMBL; LC127182; BAV69314.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1E1FFN5; -.
DR SMR; A0A1E1FFN5; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 3: Inferred from homology;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..279
FT /note="Methyltransferase prhM"
FT /id="PRO_0000449177"
FT BINDING 124..125
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
FT BINDING 152..153
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
SQ SEQUENCE 279 AA; 31760 MW; 6CE88413FCAE2C38 CRC64;
MHPDAQLKTA LKNGFDPKLL YKEPLTTVKE PVCSILEKHS KVPVDKVVSH VNEVRDRAFA
VFPYACIGQF SFVELSIADS PCYREMLERT KQGHKLLDLG CAFGQELRQL IYDGTPPTNL
YGSDIQQDFL SLGYELFLDR AILPDSQLIA ADVLDKQSAL FQRLAGELNI VYISLFLHVF
DFEKQITVAQ NVLDLLKAEP GSMIVCRVTA CRDQEVLAAT QERMPYYYHD LASWNRLWEE
VQKQTGVKLS VESWEQPDEL VKKHPLPGIY ILGSSIRRL
