ID   ADRK_PENRO              Reviewed;         278 AA.
AC   A0A1Y0BRG0;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2017, sequence version 1.
DT   03-AUG-2022, entry version 8.
DE   RecName: Full=Methyltransferase adrK {ECO:0000303|PubMed:28529508};
DE            EC=2.1.3.- {ECO:0000305|PubMed:28529508};
DE   AltName: Full=Andrastin A biosynthesis cluster protein K {ECO:0000303|PubMed:28529508};
GN   Name=adrK {ECO:0000303|PubMed:28529508};
OS   Penicillium roqueforti.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5082;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=CECT 2905;
RX   PubMed=28529508; DOI=10.3389/fmicb.2017.00813;
RA   Rojas-Aedo J.F., Gil-Duran C., Del-Cid A., Valdes N., Alamos P., Vaca I.,
RA   Garcia-Rico R.O., Levican G., Tello M., Chavez R.;
RT   "The biosynthetic gene cluster for andrastin A in Penicillium roqueforti.";
RL   Front. Microbiol. 8:813-813(2017).
CC   -!- FUNCTION: Methyltransferase; part of the gene cluster that mediates the
CC       biosynthesis of andrastins, meroterpenoid compounds that exhibit
CC       inhibitory activity against ras farnesyltransferase, suggesting that
CC       they could be promising leads for antitumor agents (PubMed:28529508).
CC       The first step of the pathway is the synthesis of 3,5-
CC       dimethylorsellinic acid (DMOA) by the polyketide synthase adrD via
CC       condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units
CC       and 2 methylations (By similarity). DMAO is then converted to farnesyl-
CC       DMAO by the prenyltransferase adrG (By similarity). The
CC       methyltransferase adrK catalyzes the methylation of the carboxyl group
CC       of farnesyl-DMAO to farnesyl-DMAO methyl ester which is further
CC       converted to epoxyfarnesyl-DMAO methyl ester by the FAD-dependent
CC       monooxygenase adrH (By similarity). The terpene cyclase adrI then
CC       catalyzes the carbon skeletal rearrangement to generate the andrastin
CC       E, the first compound in the pathway having the andrastin scaffold,
CC       with the tetracyclic ring system (By similarity). The post-cyclization
CC       tailoring enzymes adrF, adrE, adrJ, and adrA, are involved in the
CC       conversion of andrastin E into andrastin A. The short chain
CC       dehydrogenase adrF is responsible for the oxidation of the C-3 a
CC       hydroxyl group of andrastin E to yield the corresponding ketone,
CC       andrastin D. The ketoreductase adrE stereoselectively reduces the
CC       carbonyl moiety to reverse the stereochemistry of the C-3 position to
CC       yield andrastin F. The acetyltransferase adrJ is the acetyltransferase
CC       that attaches the acetyl group to the C-3 hydroxyl group of andrastin F
CC       to yield andrastin C. Finally, the cytochrome P450 monooxygenase adrA
CC       catalyzes two sequential oxidation reactions of the C-23 methyl group,
CC       to generate the corresponding alcohol andrastin B, and aldehyde
CC       andrastin A (By similarity). {ECO:0000250|UniProtKB:B6HV39,
CC       ECO:0000269|PubMed:28529508}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:28529508}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q3J7D1}.
CC   -!- DISRUPTION PHENOTYPE: Drastically reduces the production of andrastin
CC       A. {ECO:0000269|PubMed:28529508}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. {ECO:0000305}.
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DR   EMBL; KY349137; ART41216.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A1Y0BRG0; -.
DR   SMR; A0A1Y0BRG0; -.
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..278
FT                   /note="Methyltransferase adrK"
FT                   /id="PRO_0000446499"
FT   BINDING         124..125
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q3J7D1"
FT   BINDING         151..152
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   278 AA;  31586 MW;  F7E784726F33E1C2 CRC64;
     MHPDSQLETA VKNGFDPKSL YSTELTKVNE PARTILEQYS KIPAEKVLQH VKDLKDRAFE
     VFPYACIGQA SFLELSIASS PCYPEMLDRV KKGDRLLDLG CAFGQELRQL IYDGAPSQNL
     YGTDLRPEFL ELGLDLFLDR SFIKSHFIDA DVLDDKSALV TQLTGELNIV YISLFLHVFD
     FETQIKVAKR VLDLLAPKAG SLIVCRVVAC RDQAIGNATN ARLPYYYHDL ASWNRLWERV
     QEETGLKLKV DNWEQDDALA KKHPLEGIYM LGSSIRRE