ID   DMR12_CRYX8             Reviewed;         246 AA.
AC   A0A4P8DJY5;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   31-JUL-2019, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=Short chain dehydrogenase/reductase dmxR12 {ECO:0000303|PubMed:30996871};
DE            Short=SDR dmxR12 {ECO:0000303|PubMed:30996871};
DE            EC=1.1.1.- {ECO:0000305|PubMed:30996871};
DE   AltName: Full=Dimeric xanthone biosynthesis cluster protein R12 {ECO:0000303|PubMed:30996871};
GN   Name=dmxR12 {ECO:0000303|PubMed:30996871};
OS   Cryptosporiopsis sp. (strain 8999).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes;
OC   Helotiales; Dermateaceae; Cryptosporiopsis; unclassified Cryptosporiopsis.
OX   NCBI_TaxID=2572248;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=8999;
RX   PubMed=30996871; DOI=10.1039/c8sc05126g;
RA   Greco C., de Mattos-Shipley K., Bailey A.M., Mulholland N.P., Vincent J.L.,
RA   Willis C.L., Cox R.J., Simpson T.J.;
RT   "Structure revision of cryptosporioptides and determination of the genetic
RT   basis for dimeric xanthone biosynthesis in fungi.";
RL   Chem. Sci. 10:2930-2939(2019).
CC   -!- FUNCTION: Short chain dehydrogenase/reductase; part of the gene cluster
CC       that mediates the biosynthesis of the dimeric xanthones
CC       cryptosporioptides (PubMed:30996871). The pathway begins with the
CC       synthesis of atrochrysone thioester by the polyketide synthase dmx-
CC       nrPKS (Probable). The atrochrysone carboxyl ACP thioesterase dmxR1 then
CC       breaks the thioester bond and releases the atrochrysone carboxylic acid
CC       from dmx-nrPKS (Probable). Atrochrysone carboxylic acid is
CC       decarboxylated by the decarboxylase dmxR15, and oxidized by the
CC       anthrone oxygenase dmxR16 to yield emodin (Probable). Emodin is then
CC       reduced to emodin hydroquinone by the oxidoreductase dmxR7 (Probable).
CC       A-ring reduction by the short chain dehydrogenase dmxR18, dehydration
CC       by the scytalone dehydratase-like protein dmxR17 and probable
CC       spontaneous re-oxidation, results in overall deoxygenation to
CC       chrysophanol (PubMed:30996871). Baeyer-Villiger oxidation by the
CC       Baeyer-Villiger monooxygenase (BVMO) dmxR6 then yields monodictylactone
CC       in equilibrium with monodictyphenone (PubMed:30996871). In the case of
CC       the cryptosporioptides biosynthesis, monodictylactone is reduced at C-
CC       12 to an alcohol (by the short chain dehydrogenases dmxR12 or dmxR8)
CC       and hydroxylated at C-5 by dmxR9, yielding the electron-rich aromatic
CC       which could eliminate H(2)O to form the ortho-quinonemethide, followed
CC       by tautomerisation to paraquinone and complete the formal reduction to
CC       produce the 10-methylgroup (Probable). Conjugate addition of C-4a-OH to
CC       the resulting paraquinone by the monooxygenase dmxR10 then gives
CC       cyclohexadienone, which is then reduced at C-5 by the short chain
CC       dehydrogenase dmxR3 to give the dihydroxanthone (Probable). The 6,7-
CC       epoxide in the cryptosporioptides could be introduced by the cytochrome
CC       P450 monooxygenase dmxL3 (Probable). The highly reducing PKS dmxL2
CC       manufactures butyrate, which is further carboxylated by dmxL1 to form
CC       ethylmalonate (PubMed:30996871). It is not yet clear whether the
CC       carboxylation occurs while the butyrate is attached to the ACP of
CC       dmxL2, but this unusual fungal metabolite could then be esterified to
CC       O-5 by the O-acetyltransferase dmxR13 (PubMed:30996871). Finally,
CC       dimerization performed by dmxR5 gives the observed dimers
CC       cryptosporioptides A, B and C as the final products of the pathway
CC       (PubMed:30996871). {ECO:0000269|PubMed:30996871,
CC       ECO:0000305|PubMed:30996871}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:30996871}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; MK182094; QCL09103.1; -; Genomic_DNA.
DR   SMR; A0A4P8DJY5; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   NADP; Oxidoreductase.
FT   CHAIN           1..246
FT                   /note="Short chain dehydrogenase/reductase dmxR12"
FT                   /id="PRO_0000453448"
FT   ACT_SITE        164
FT                   /note="Lowers pKa of active site Tyr"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         12..15
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         35..37
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         64..65
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
FT   BINDING         164
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:O93868"
SQ   SEQUENCE   246 AA;  26267 MW;  9F9F51D32558BF2B CRC64;
     MSSPIVLIFG AGANIGYNVA KEFVASGYKA VLTSRKAPTE PDASFSYVQG DLSDPKSVTD
     TFSQVRKQFG EPSVVVYNGN SKWHSNKEIA AAVSFTAKED PFVVDLPTFE KDLNINTTST
     FVAIKEALAS FAALPETASR TFIYTGNAMN FLPFGGAMTL GAGKSASAHM IAAAAAAYAP
     KGYKFYYPDE RQPDGRLGGR GISGEAHAKI YKKLSEDKTQ GPWLQTFVKG TGYVSFPADT
     DVSVAH