ID   DNRE_STRS5              Reviewed;         251 AA.
AC   Q53882;
DT   19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-AUG-2022, entry version 87.
DE   RecName: Full=Aklaviketone reductase DauE;
DE            EC=1.1.1.362;
GN   Name=dauE;
OS   Streptomyces sp. (strain C5).
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=45212;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   SUBSTRATE SPECIFICITY.
RC   STRAIN=C5;
RX   PubMed=8655529; DOI=10.1128/jb.178.11.3384-3388.1996;
RA   Dickens M.L., Ye J., Strohl W.R.;
RT   "Cloning, sequencing, and analysis of aklaviketone reductase from
RT   Streptomyces sp. strain C5.";
RL   J. Bacteriol. 178:3384-3388(1996).
RN   [2]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=2584139; DOI=10.7164/antibiotics.42.1567;
RA   Pandey R.C., Toussaint M.W., McGuire J.C., Thomas M.C.;
RT   "Maggiemycin and anhydromaggiemycin: two novel anthracyclinone antitumor
RT   antibiotics. Isolation, structures, partial synthesis and biological
RT   properties.";
RL   J. Antibiot. 42:1567-1577(1989).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=C5;
RA   Bartel P.L., Connors N.C., William R.S.;
RT   "Biosynthesis of anthracyclines: analysis of mutants of Streptomyces sp.
RT   strain C5 blocked in daunomycin biosynthesis.";
RL   J. Gen. Microbiol. 136:1877-1886(1990).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=C5;
RA   Connors N.C., Bartel P.L., William R.S.;
RT   "Biosynthesis of anthracyclines: enzymic conversion of aklanonic acid to
RT   aklavinone and epsilon-rhodomycinone by anthracycline-producing
RT   streptomycetes.";
RL   J. Gen. Microbiol. 136:1887-1894(1990).
CC   -!- FUNCTION: Involved in the biosynthesis of aklavinone which is an
CC       important precursor common to the formation of the clinically
CC       significant anthracyclines such as carminomycin, daunorubicin
CC       (daunomycin), rhodomycin, aclacinomycin T (aklavin) and aclacinomycin A
CC       (aclarubicin). These compounds are aromatic polyketide antibiotics that
CC       exhibit high cytotoxicity and are widely applied in the chemotherapy of
CC       a variety of cancers. Catalyzes the NADPH-specific conversion of
CC       aklaviketone to yield aklavinone. It can also convert maggiemycin and
CC       7-oxodaunomycinone to epsilon-rhodomycinone and daunomycinone,
CC       respectively. {ECO:0000269|PubMed:2584139, ECO:0000269|PubMed:8655529,
CC       ECO:0000269|Ref.3, ECO:0000269|Ref.4}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=aklavinone + NADP(+) = aklaviketone + 2 H(+) + NADPH;
CC         Xref=Rhea:RHEA:37411, ChEBI:CHEBI:15378, ChEBI:CHEBI:31181,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:77994;
CC         EC=1.1.1.362; Evidence={ECO:0000269|PubMed:8655529};
CC   -!- PATHWAY: Antibiotic biosynthesis; daunorubicin biosynthesis.
CC   -!- PATHWAY: Antibiotic biosynthesis; carminomycin biosynthesis.
CC   -!- PATHWAY: Antibiotic biosynthesis; rhodomycin biosynthesis.
CC   -!- PATHWAY: Antibiotic biosynthesis; aclacinomycin biosynthesis.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene accumulate maggiemycin.
CC       In the absence of the aklavinone intermediate, aklaviketone is
CC       apparently hydroxylated at C-11 to form maggiemycin.
CC       {ECO:0000269|PubMed:2584139, ECO:0000269|Ref.3, ECO:0000269|Ref.4}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; U43704; AAB08021.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q53882; -.
DR   SMR; Q53882; -.
DR   KEGG; ag:AAB08021; -.
DR   BioCyc; MetaCyc:MON-18180; -.
DR   BRENDA; 1.1.1.362; 1284.
DR   UniPathway; UPA00054; -.
DR   UniPathway; UPA01040; -.
DR   UniPathway; UPA01042; -.
DR   UniPathway; UPA01043; -.
DR   GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:UniProtKB.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IDA:UniProtKB.
DR   GO; GO:1901771; P:daunorubicin biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0044598; P:doxorubicin metabolic process; IDA:UniProtKB.
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   Antibiotic biosynthesis; NADP; Oxidoreductase.
FT   CHAIN           1..251
FT                   /note="Aklaviketone reductase DauE"
FT                   /id="PRO_0000425674"
FT   ACT_SITE        152
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         58..59
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         86
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         152..156
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
FT   BINDING         185
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   251 AA;  25632 MW;  64E53501FECC2847 CRC64;
     MENTQRSVIV TGGGSGIGRA VARAFAARGD RVLVVGRTAG PLAETVDGHK EAHTLAVDIT
     DPAAPQAVVR EVRERLGGVV DVLVNNAATA VFGHLGELDR TAVEAQVATN LVAPVLLTQA
     LLDPLETASG LVVNIGSAGA LGRRAWPGNA VYGAAKAGLD LLTRSWAVEL GPRGIRVIGV
     APGVIETGAG VRAGMSQEAY DGFLEAMGQR VPLGRVGRPE DVAWWVVRLA DPEAAYASGA
     VLAVDGGLSV T