ID   AUSK_PENBI              Reviewed;         398 AA.
AC   A0A0F7TN16;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   22-JUL-2015, sequence version 1.
DT   03-AUG-2022, entry version 24.
DE   RecName: Full=Aldo-keto reductase ausK {ECO:0000303|PubMed:29076725};
DE            EC=1.1.1.- {ECO:0000305|PubMed:29076725};
DE   AltName: Full=Austinoid biosynthesis clusters protein K {ECO:0000303|PubMed:29076725};
GN   Name=ausK {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_06818;
OS   Penicillium brasilianum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=104259;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MG11;
RX   PubMed=26337871; DOI=10.1128/genomea.00724-15;
RA   Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Brakhage A.A.,
RA   Valiante V.;
RT   "Draft genome sequence of the fungus Penicillium brasilianum MG11.";
RL   Genome Announc. 3:0-0(2015).
RN   [2]
RP   FUNCTION.
RX   PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA   Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA   Zhang H., Hayashi F., Abe I.;
RT   "Discovery of key dioxygenases that diverged the paraherquonin and
RT   acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL   J. Am. Chem. Soc. 138:12671-12677(2016).
RN   [3]
RP   FUNCTION.
RX   PubMed=29076725; DOI=10.1021/acschembio.7b00814;
RA   Mattern D.J., Valiante V., Horn F., Petzke L., Brakhage A.A.;
RT   "Rewiring of the austinoid biosynthetic pathway in filamentous fungi.";
RL   ACS Chem. Biol. 12:2927-2933(2017).
CC   -!- FUNCTION: Aldo-keto reductase; part of the gene cluster B that mediates
CC       the biosynthesis of the fungal meroterpenoid acetoxydehydroaustin
CC       (PubMed:29076725). The first step of the pathway is the synthesis of
CC       3,5-dimethylorsellinic acid by the polyketide synthase ausA (By
CC       similarity). 3,5-dimethylorsellinic acid is then prenylated by the
CC       polyprenyl transferase ausN (By similarity). Further epoxidation by the
CC       FAD-dependent monooxygenase ausM and cyclization by the probable
CC       terpene cyclase ausL lead to the formation of protoaustinoid A (By
CC       similarity). Protoaustinoid A is then oxidized to spiro-lactone
CC       preaustinoid A3 by the combined action of the FAD-binding
CC       monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity).
CC       Acid-catalyzed keto-rearrangement and ring contraction of the
CC       tetraketide portion of preaustinoid A3 by ausJ lead to the formation of
CC       preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the
CC       help of ausH, is involved in the next step by transforming preaustinoid
CC       A4 into isoaustinone which is in turn hydroxylated by the P450
CC       monooxygenase ausI to form austinolide (By similarity). The cytochrome
CC       P450 monooxygenase ausG then modifies austinolide to austinol (By
CC       similarity). Austinol is further acetylated to austin by the O-
CC       acetyltransferase ausP, which spontaneously changes to dehydroaustin
CC       (PubMed:29076725). The cytochrome P450 monooxygenase then converts
CC       dehydroaustin is into 7-dehydrodehydroaustin (PubMed:29076725). The
CC       hydroxylation catalyzed by ausR permits the second O-acetyltransferase
CC       ausQ to add an additional acetyl group to the molecule, leading to the
CC       formation of acetoxydehydroaustin (PubMed:29076725). Due to genetic
CC       rearrangements of the clusters and the subsequent loss of some enzymes,
CC       the end product of the Penicillium brasilianum austinoid biosynthesis
CC       clusters is acetoxydehydroaustin (PubMed:29076725).
CC       {ECO:0000250|UniProtKB:C8VQ93, ECO:0000269|PubMed:29076725}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305|PubMed:29076725}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8CG76}.
CC   -!- MISCELLANEOUS: In A.calidoustus, the austinoid gene cluster lies on a
CC       contiguous DNA region, while clusters from E.nidulans and P.brasilianum
CC       are split in their respective genomes. Genetic rearrangements provoked
CC       variability among the clusters and E.nidulans produces the least number
CC       of austionoid derivatives with the end products austinol and
CC       dehydroaustinol, while P.brasilianum can produce until
CC       acetoxydehydroaustin, and A.calidoustus produces the highest number of
CC       identified derivatives. {ECO:0000305|PubMed:29076725}.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC       reductase 2 subfamily. {ECO:0000305}.
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DR   EMBL; CDHK01000006; CEJ58148.1; -; Genomic_DNA.
DR   SMR; A0A0F7TN16; -.
DR   EnsemblFungi; CEJ58148; CEJ58148; PMG11_06818.
DR   OrthoDB; 706185at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000042958; Unassembled WGS sequence.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.20.20.100; -; 1.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   SUPFAM; SSF51430; SSF51430; 1.
PE   3: Inferred from homology;
KW   NADP; Oxidoreductase; Reference proteome.
FT   CHAIN           1..398
FT                   /note="Aldo-keto reductase ausK"
FT                   /id="PRO_0000453855"
FT   ACT_SITE        81
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT   BINDING         76
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O43488"
FT   BINDING         156
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT   BINDING         186..187
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O43488"
FT   BINDING         212
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O43488"
FT   BINDING         241..251
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O43488"
FT   BINDING         317..325
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O43488"
SQ   SEQUENCE   398 AA;  43689 MW;  67492640E4058B33 CRC64;
     MTGTRILELF GPAPEPPSEL GRYRILSPTA GIRVSPLQLG ALSIGDAWST DLGSMDKDSA
     MELLDAYAAS GGNFIDTANG YQNEQSETWI GEWMASRTNR DQMVIATKFG PDYRAHELGK
     GLPVNYSGNH KRSLHMSVRD SLRKLQTSWI DILYLHTWDY TTSIPELMDS LHHLVQRGEV
     LYLGICNTPA WVVSAANTYA QQQGKTQFSV YQGRWNPLRR EIERDILPMA RHFGMAVTVY
     DALGSGKFQS RDMLARRKDQ GEGLRAIYGG EQTALEEAMS KALGVVAAQH GTESVTAVAL
     AYLLAKAPYV FPIIGGRKIQ HLHDNIQALS LRLSQEEIKY LESVGDFDPG FPYDMAGVDP
     ADTGIATPIV AQAAPMAFVQ RSKAIGYAES NKGSQTSG