ADRF_PENRO
ID ADRF_PENRO Reviewed; 256 AA.
AC A0A1Y0BRF8;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=Short chain dehydrogenase adrF {ECO:0000303|PubMed:28529508};
DE EC=1.1.1.- {ECO:0000305|PubMed:28529508};
DE AltName: Full=Andrastin A biosynthesis cluster protein F {ECO:0000303|PubMed:28529508};
GN Name=adrF {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: 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
CC (PubMed:28529508). The first step of the pathway is the synthesis of
CC 3,5-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:B6HV34,
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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; KY349137; ART41211.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1Y0BRF8; -.
DR SMR; A0A1Y0BRF8; -.
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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW NAD; Oxidoreductase.
FT CHAIN 1..256
FT /note="Short chain dehydrogenase adrF"
FT /id="PRO_0000446482"
FT ACT_SITE 151
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 138
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 151..155
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 184..186
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 256 AA; 27022 MW; 2F8E169B092FE7A4 CRC64;
MSLLQDIVVI ITGSASGIGL ATATAALSQG ARILGVDVSS APVSLNEHPN YKFMQGDLTH
ETTPRQVVET CIKEFGGRID GLLNIAGIMD QNSSVDSLSD YMWERCIAVN LTAPVKLMRE
VIPIMRQQQS GSIVNVGSKA ATSGASSGVA YTASKHGLMG ATKNVAWRYK QEGIRCNAVC
PGGVPTGIVQ ASDPSTWDKD ALGTMSLIHQ AHAADRQKGL GVEAEDIADC LLFLISSQSK
RINGAIIPID NAWSVI
