ID   ADRE_PENRO              Reviewed;         336 AA.
AC   A0A1Y0BRF3;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   30-AUG-2017, sequence version 1.
DT   03-AUG-2022, entry version 11.
DE   RecName: Full=Ketoreductase adrE {ECO:0000303|PubMed:28529508};
DE            EC=1.1.1.- {ECO:0000305|PubMed:28529508};
DE   AltName: Full=Andrastin A biosynthesis cluster protein E {ECO:0000303|PubMed:28529508};
GN   Name=adrE {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: Ketoreductase; 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:B6HV33,
CC       ECO:0000269|PubMed:28529508}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:28529508}.
CC   -!- DISRUPTION PHENOTYPE: Drastically reduces the production of andrastin
CC       A. {ECO:0000269|PubMed:28529508}.
CC   -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC       family. Dihydroflavonol-4-reductase subfamily. {ECO:0000305}.
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DR   EMBL; KY349137; ART41210.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A1Y0BRF3; -.
DR   SMR; A0A1Y0BRF3; -.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR001509; Epimerase_deHydtase.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   Pfam; PF01370; Epimerase; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   Oxidoreductase.
FT   CHAIN           1..336
FT                   /note="Ketoreductase adrE"
FT                   /id="PRO_0000446477"
FT   BINDING         171
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:A0A059TC02"
SQ   SEQUENCE   336 AA;  36698 MW;  2EC57CBDAA60369A CRC64;
     MTQAQNYVIP PGSKVLVTGA NGYIASHIVK ALLDLGYLVR GTVRTPMPWL AEYFERQCGL
     GRFELIVVSD FQQPDAFDES VKGVSGVIHV AQGLPSSTAA ETVKSATAYT VNGVINLFKA
     ASTQRTIQRV VLTSSIVAAG YPTGKGFKLD ADSWDESLEQ ASKDGTTVPI YRACKIEGER
     QAWKWVEKNQ PHFELNSVLP WLTLGKILHP NIGGSTMGYV SGLLRGDTTP FKFLPLPWFV
     DVEDTARLHA IALLNPSVRS ERLFATAAPF TWGDVIEILK RIQPNNARIP AAPIQEEPTL
     GDVVPAARAE KLLRETFGQL GWTPLEVSLE SGIARE