ID   SDNK_SORAA              Reviewed;         351 AA.
AC   A0A1B4XBH5;
DT   30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2016, sequence version 1.
DT   03-AUG-2022, entry version 12.
DE   RecName: Full=Short-chain dehydrogenase sdnK {ECO:0000303|PubMed:27072286};
DE            EC=1.1.1.- {ECO:0000305|PubMed:27072286};
DE   AltName: Full=Sordarin/hypoxysordarin biosynthesis cluster protein K {ECO:0000303|PubMed:27072286};
GN   Name=sdnK {ECO:0000303|PubMed:27072286};
OS   Sordaria araneosa (Pleurage araneosa).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Sordariaceae; Sordaria.
OX   NCBI_TaxID=573841;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=ATCC 36386 / NRRL 3196;
RX   PubMed=27072286; DOI=10.1038/ja.2016.40;
RA   Kudo F., Matsuura Y., Hayashi T., Fukushima M., Eguchi T.;
RT   "Genome mining of the sordarin biosynthetic gene cluster from Sordaria
RT   araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and
RT   GDP-6-deoxyaltrose transferase.";
RL   J. Antibiot. 69:541-548(2016).
CC   -!- FUNCTION: Short-chain dehydrogenase; part of the gene cluster that
CC       mediates the biosynthesis of sordarin and hypoxysordarin, glycoside
CC       antibiotics with a unique tetracyclic diterpene aglycone structure
CC       (PubMed:27072286). First, the geranylgeranyl diphosphate synthase sdnC
CC       constructs GGDP from farnesyl diphosphate and isopentenyl diphosphate
CC       (PubMed:27072286). The diterpene cyclase sdnA then catalyzes the
CC       cyclization of GGDP to afford cycloaraneosene (PubMed:27072286).
CC       Cycloaraneosene is then hydroxylated four times by the putative
CC       cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH to give a
CC       hydroxylated cycloaraneosene derivative such as cycloaraneosene-
CC       8,9,13,19-tetraol (PubMed:27072286). Although the order of the
CC       hydroxylations is unclear, at least C8, C9 and C13 of the
CC       cycloaraneosene skeleton are hydroxylated before the sordaricin
CC       formation (PubMed:27072286). Dehydration of the 13-hydroxy group of the
CC       hydroxylated cycloaraneosene derivative might be catalyzed by an
CC       unassigned hypothetical protein such as sdnG and sdnP to construct the
CC       cyclopentadiene moiety (PubMed:27072286). The FAD-dependent
CC       oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the
CC       hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-
CC       Villiger oxidation to give the lactone intermediate (PubMed:27072286).
CC       The presumed lactone intermediate would be hydrolyzed to give an
CC       acrolein moiety and a carboxylate moiety (PubMed:27072286). Then,
CC       [4+2]cycloaddition would occur between the acrolein moiety and the
CC       cyclopentadiene moiety to give sordaricin (PubMed:27072286). SdnN might
CC       also be involved in the [4+2]cycloaddition after the hypothesized
CC       oxidation to accommodate the oxidized product and prompt the
CC       [4+2]cycloaddition (PubMed:27072286). GDP-6-deoxy-D-altrose may be
CC       biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-
CC       dehydratase sdnI and the short-chain dehydrogenase sdnK
CC       (PubMed:27072286). The glycosyltransferase sdnJ catalyzes the
CC       attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin
CC       to give 4'-O-demethylsordarin (PubMed:27072286). The methyltransferase
CC       sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
CC       Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
CC       The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would
CC       be constructed by an iterative type I PKS sdnO and the trans-acting
CC       polyketide methyltransferase sdnL. SdnL would be responsible for the
CC       introduction of an alpha-methyl group of the polyketide chain
CC       (PubMed:27072286). Alternatively, the beta-lactamase-like protein sdnR
CC       might be responsible for the cleavage and transfer of the polyketide
CC       chain from the PKS sdnO to sordarin (PubMed:27072286). Two putative
CC       cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the
CC       epoxidations of the polyketide chain to complete the biosynthesis of
CC       hypoxysordarin (PubMed:27072286). Transcriptional regulators sdnM and
CC       sdnS are presumably encoded for the transcriptional regulation of the
CC       expression of the sdn gene cluster (PubMed:27072286).
CC       {ECO:0000269|PubMed:27072286}.
CC   -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:27072286}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; LC079035; BAV32155.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A1B4XBH5; -.
DR   SMR; A0A1B4XBH5; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   Antibiotic biosynthesis; NAD; Oxidoreductase.
FT   CHAIN           1..351
FT                   /note="Short-chain dehydrogenase sdnK"
FT                   /id="PRO_0000441062"
FT   ACT_SITE        224
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         38..46
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         65..66
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         123..125
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         224..228
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         266..268
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
SQ   SEQUENCE   351 AA;  38070 MW;  AAD2FD046F2AAA8F CRC64;
     MVQFNGPHGK VTVSYLRQGG LNPPAPAPKG SFTGKTVLIT GCSSGIGYQA ALQIASLNPK
     RLILGTRTLA KGEAAKQEIL ATVGPSLDSS IIEVIPIECS DLSSVRQFTT TVRKTTPPGT
     LDCVLLSAGL ALPTREVVTD ESGHEWPTTF VVNVLAPALL ALEFLPLLQS TPGSVVESVN
     SISYCNVTSE DISPLLSSQD EATGTTSALD FFNNPERWTT QRAYYEAKLM LMFVLEGLVQ
     DQAQQQASQP GEDRKVLFLA CCPGQCRTNL YRQFGLGVRA FMTLFNAVIA RTAEQGARTL
     VTGLLLQGEE AMGKMWVNDR FDDWSPGITE EEWKVLQKRV WEEIKGVLGK A