ID   AUST_ASPCI              Reviewed;         411 AA.
AC   A0A0U5GGX2;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   16-MAR-2016, sequence version 1.
DT   03-AUG-2022, entry version 14.
DE   RecName: Full=Short chain dehydrogenase ausT {ECO:0000303|PubMed:28233494};
DE            EC=1.1.1.- {ECO:0000269|PubMed:28233494};
DE   AltName: Full=Austinoid biosynthesis cluster protein T {ECO:0000303|PubMed:28233494};
GN   Name=ausT {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14362;
OS   Aspergillus calidoustus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=454130;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=SF006504;
RX   PubMed=26966204; DOI=10.1128/genomea.00102-16;
RA   Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Scherlach K.,
RA   Martin K., Brakhage A.A., Petzke L., Valiante V.;
RT   "Draft genome sequences of fungus Aspergillus calidoustus.";
RL   Genome Announc. 4:0-0(2016).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=28233494; DOI=10.1021/acschembio.7b00003;
RA   Valiante V., Mattern D.J., Schueffler A., Horn F., Walther G.,
RA   Scherlach K., Petzke L., Dickhaut J., Guthke R., Hertweck C., Nett M.,
RA   Thines E., Brakhage A.A.;
RT   "Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus
RT   calidoustus.";
RL   ACS Chem. Biol. 12:1227-1234(2017).
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: Short chain dehydrogenase; part of the gene cluster that
CC       mediates the biosynthesis of calidodehydroaustin, a fungal
CC       meroterpenoid (PubMed:28233494, PubMed:29076725). The first step of the
CC       pathway is the synthesis of 3,5-dimethylorsellinic acid by the
CC       polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid
CC       is then prenylated by the polyprenyl transferase ausN
CC       (PubMed:28233494). Further epoxidation by the FAD-dependent
CC       monooxygenase ausM and cyclization by the probable terpene cyclase ausL
CC       lead to the formation of protoaustinoid A (By similarity).
CC       Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by
CC       the combined action of the FAD-binding monooxygenases ausB and ausC,
CC       and the dioxygenase ausE (By similarity). Acid-catalyzed keto-
CC       rearrangement and ring contraction of the tetraketide portion of
CC       preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By
CC       similarity). The aldo-keto reductase ausK, with the help of ausH, is
CC       involved in the next step by transforming preaustinoid A4 into
CC       isoaustinone which is in turn hydroxylated by the P450 monooxygenase
CC       ausI to form austinolide (By similarity). The cytochrome P450
CC       monooxygenase ausG modifies austinolide to austinol (By similarity).
CC       Austinol is further acetylated to austin by the O-acetyltransferase
CC       ausP, which spontaneously changes to dehydroaustin (PubMed:28233494).
CC       The cytochrome P450 monooxygenase ausR then converts dehydroaustin is
CC       into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation
CC       catalyzed by ausR permits the O-acetyltransferase ausQ to add an
CC       additional acetyl group to the molecule, leading to the formation of
CC       acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase
CC       ausT catalyzes the reduction of the double bond present between carbon
CC       atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-
CC       hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an
CC       acetylation reaction but also the addition of the PKS ausV diketide
CC       product to 1,2-dihydro-7-hydroxydehydroaustin, forming
CC       precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-
CC       ketoglutarate-dependent dioxygenase converts precalidodehydroaustin
CC       into calidodehydroaustin (PubMed:28233494).
CC       {ECO:0000250|UniProtKB:Q5ATJ7, ECO:0000269|PubMed:28233494,
CC       ECO:0000269|PubMed:29076725}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:28233494}.
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 short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; CDMC01000024; CEL11259.1; -; Genomic_DNA.
DR   SMR; A0A0U5GGX2; -.
DR   EnsemblFungi; CEL11259; CEL11259; ASPCAL14362.
DR   OrthoDB; 1143475at2759; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000054771; 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   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   NAD; Oxidoreductase; Reference proteome.
FT   CHAIN           1..411
FT                   /note="Short chain dehydrogenase ausT"
FT                   /id="PRO_0000453871"
FT   ACT_SITE        215
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:A0A1E1FFP5"
FT   BINDING         15..17
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT   BINDING         43..44
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT   BINDING         66..67
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT   BINDING         137
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT   BINDING         203
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
FT   BINDING         211..213
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PQJ9"
SQ   SEQUENCE   411 AA;  46849 MW;  0FCED3863BE12CB4 CRC64;
     MVDKSNKVAL VLGATGISGW ALAKNALSYP SRSTFQRVIG LMHRPRTVEE TGLPNDPRLE
     LYSGVDLQGD LNHVVVKLKE KIPRIEEVTH VYYLAYMTLQ TCSGDMRQFR DANVAMTYTA
     VHACDRLCPN MEFFVLQTGT NAYGVACFDY LRQTQLQVPL RESNPRVPRP WSDTLFYYAQ
     ADLIKEANKG KAWKWCEVRP DQIVGHTPAQ VSVPYVAPMA LYLALYRYIN GPGARVQFPG
     TVRNYHHTYT DVRPDTMARA ELYLSLVKSD ESHGEAFNIA DTDTPGPWSA KWPSICRYFG
     LEASETIDDE WTDIDGWWYA NQTAYERMCA EYGLQKQVMS PTAWSLMKMG HTLIDQNREL
     CLDKIRGLGF TEDHPVGSSY FQVFEDFERM KIIPPKVVLA SPRCRDVLHQ C