ADRF_PENRW
ID ADRF_PENRW Reviewed; 255 AA.
AC B6HV34;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Short chain dehydrogenase adrF {ECO:0000303|Ref.2};
DE EC=1.1.1.- {ECO:0000269|Ref.2};
DE AltName: Full=Andrastin A biosynthesis cluster protein F {ECO:0000303|Ref.2};
GN Name=adrF {ECO:0000303|Ref.2}; ORFNames=Pc22g22870;
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: Short chain dehydrogenase; part of the gene cluster that
CC mediates the biosynthesis of andrastins, meroterpenoid compounds that
CC exhibit inhibitory activity against ras farnesyltransferase, suggesting
CC that they could be promising leads for antitumor agents (Ref.2). The
CC first step of the pathway is the synthesis of 3,5-dimethylorsellinic
CC acid (DMOA) by the polyketide synthase adrD via condensation of one
CC acetyl-CoA starter unit with 3 malonyl-CoA units and 2 methylations
CC (Ref.2). DMAO is then converted to farnesyl-DMAO by the
CC prenyltransferase adrG (Ref.2). The methyltransferase adrK catalyzes
CC the methylation of the carboxyl group of farnesyl-DMAO to farnesyl-DMAO
CC methyl ester which is further converted to epoxyfarnesyl-DMAO methyl
CC ester by the FAD-dependent monooxygenase adrH (Ref.2). The terpene
CC cyclase adrI then catalyzes the carbon skeletal rearrangement to
CC generate the andrastin E, the first compound in the pathway having the
CC andrastin scaffold, with the tetracyclic ring system (Ref.2). The post-
CC cyclization tailoring enzymes adrF, adrE, adrJ, and adrA, are involved
CC in the 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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; AM920437; CAP99575.1; -; Genomic_DNA.
DR RefSeq; XP_002566181.1; XM_002566135.1.
DR AlphaFoldDB; B6HV34; -.
DR SMR; B6HV34; -.
DR STRING; 1108849.XP_002566181.1; -.
DR EnsemblFungi; CAP99575; CAP99575; PCH_Pc22g22870.
DR GeneID; 8309013; -.
DR KEGG; pcs:Pc22g22870; -.
DR VEuPathDB; FungiDB:PCH_Pc22g22870; -.
DR eggNOG; KOG0725; Eukaryota.
DR HOGENOM; CLU_010194_1_0_1; -.
DR OMA; EHAVAKC; -.
DR OrthoDB; 1226147at2759; -.
DR BioCyc; PCHR:PC22G22870-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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..255
FT /note="Short chain dehydrogenase adrF"
FT /id="PRO_0000446481"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 10..18
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 37..38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 56..58
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 137
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 150..154
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 183..185
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 255 AA; 26909 MW; 4F5C78CC4E63941B CRC64;
MSLLQDIVLI ITGSASGIGL ATATAALSQG AKILGVDVSW APVSLTEHAS YKFIQANLTH
EATPKQVVET CIKEFGRIDG LLNIAGIMDQ NSSVDSLTDD MWERCIAINL TAPVKLMREV
IPIMRQQKSG SIVNVGSKAA TSGAASGVAY TASKHGLMGA TKNVAWRYKQ EGIRCNAVCP
GGVPTGIVQA SDPTTWDKDA LATMSHIHQA HAADRQEGLG VEAEDIANCL LFLVSSQSKR
INGAIIPVDN AWSVI
