ID   ADRE_PENRW              Reviewed;         336 AA.
AC   B6HV33;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   03-AUG-2022, entry version 60.
DE   RecName: Full=Ketoreductase adrE {ECO:0000303|Ref.2};
DE            EC=1.1.1.- {ECO:0000269|Ref.2};
DE   AltName: Full=Andrastin A biosynthesis cluster protein E {ECO:0000303|Ref.2};
GN   Name=adrE {ECO:0000303|Ref.2}; ORFNames=Pc22g22860;
OS   Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS   54-1255) (Penicillium chrysogenum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC   Penicillium chrysogenum species complex.
OX   NCBI_TaxID=500485;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX   PubMed=18820685; DOI=10.1038/nbt.1498;
RA   van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA   Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA   Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA   Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA   van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA   Bovenberg R.A.L.;
RT   "Genome sequencing and analysis of the filamentous fungus Penicillium
RT   chrysogenum.";
RL   Nat. Biotechnol. 26:1161-1168(2008).
RN   [2]
RP   IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   DOI=10.1016/j.tet.2013.07.029;
RA   Matsuda Y., Awakawa T., Abe I.;
RT   "Reconstituted biosynthesis of fungal meroterpenoid andrastin A.";
RL   Tetrahedron 69:8199-8204(2013).
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 (Ref.2). The first
CC       step of the pathway is the synthesis of 3,5-dimethylorsellinic acid
CC       (DMOA) by the polyketide synthase adrD via condensation of one acetyl-
CC       CoA starter unit with 3 malonyl-CoA units and 2 methylations (Ref.2).
CC       DMAO is then converted to farnesyl-DMAO by the prenyltransferase adrG
CC       (Ref.2). The methyltransferase adrK catalyzes the methylation of the
CC       carboxyl group of farnesyl-DMAO to farnesyl-DMAO methyl ester which is
CC       further converted to epoxyfarnesyl-DMAO methyl ester by the FAD-
CC       dependent monooxygenase adrH (Ref.2). 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 (Ref.2). 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 (Ref.2). {ECO:0000269|Ref.2}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|Ref.2}.
CC   -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC       family. Dihydroflavonol-4-reductase subfamily. {ECO:0000305}.
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DR   EMBL; AM920437; CAP99574.1; -; Genomic_DNA.
DR   RefSeq; XP_002566180.1; XM_002566134.1.
DR   AlphaFoldDB; B6HV33; -.
DR   SMR; B6HV33; -.
DR   STRING; 500485.B6HV33; -.
DR   EnsemblFungi; CAP99574; CAP99574; PCH_Pc22g22860.
DR   GeneID; 8309012; -.
DR   KEGG; pcs:Pc22g22860; -.
DR   VEuPathDB; FungiDB:PCH_Pc22g22860; -.
DR   eggNOG; KOG1502; Eukaryota.
DR   HOGENOM; CLU_007383_9_2_1; -.
DR   OMA; MENIMST; -.
DR   OrthoDB; 848823at2759; -.
DR   BioCyc; PCHR:PC22G22860-MON; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000000724; Contig Pc00c22.
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   1: Evidence at protein level;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..336
FT                   /note="Ketoreductase adrE"
FT                   /id="PRO_0000446476"
FT   BINDING         171
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:A0A059TC02"
SQ   SEQUENCE   336 AA;  36557 MW;  69DCF6CF44D43955 CRC64;
     MTQAQNHIVP PGSKVLVTGA NGYIASHIIK VLLDLGYLVQ GTVRTPMPWL TEYFEKRYGS
     GRFELIVVSD FQQSDAFDES VKGVSGVIHV AQGLPSSTAA ETVESATAYT VNGVVNLLKA
     ASTKPTIKRV VLTSSIVAAG YPAGKGFKLD VDTWDKSLEQ ASKGGTTVPI YRACKVEGER
     QAWKWVEKNQ PHFELNTVLP WLTLGKILHP NIGGSTMGYV SGLLKGDTTP FKFLPLPWFV
     DVEDTARLHA IALISPSVRS ERLFAAATPF IWGDVIEILK RIQPNNARIP AAPVKEEPTI
     GDIVPAARAE KLLRETFGQR GWTPLEVSLE GGIARE