DMXR8_CRYX8
ID DMXR8_CRYX8 Reviewed; 324 AA.
AC A0A4P8DJW5;
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 dmxR8 {ECO:0000303|PubMed:30996871};
DE Short=SDR dmxR8 {ECO:0000303|PubMed:30996871};
DE EC=1.1.1.- {ECO:0000305|PubMed:30996871};
DE AltName: Full=Dimeric xanthone biosynthesis cluster protein R8 {ECO:0000303|PubMed:30996871};
GN Name=dmxR8 {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; part of the gene cluster that
CC mediates the biosynthesis of the dimeric xanthones cryptosporioptides
CC (PubMed:30996871). The pathway begins with the synthesis of
CC atrochrysone thioester by the polyketide synthase dmx-nrPKS (Probable).
CC The atrochrysone carboxyl ACP thioesterase dmxR1 then breaks the
CC thioester bond and releases the atrochrysone carboxylic acid from dmx-
CC nrPKS (Probable). Atrochrysone carboxylic acid is decarboxylated by the
CC decarboxylase dmxR15, and oxidized by the anthrone oxygenase dmxR16 to
CC yield emodin (Probable). Emodin is then reduced to emodin hydroquinone
CC by the oxidoreductase dmxR7 (Probable). A-ring reduction by the short
CC chain dehydrogenase dmxR18, dehydration by the scytalone dehydratase-
CC like protein dmxR17 and probable spontaneous re-oxidation, results in
CC overall deoxygenation to chrysophanol (PubMed:30996871). Baeyer-
CC Villiger oxidation by the Baeyer-Villiger monooxygenase (BVMO) dmxR6
CC then yields monodictylactone in equilibrium with monodictyphenone
CC (PubMed:30996871). In the case of the cryptosporioptides biosynthesis,
CC monodictylactone is reduced at C-12 to an alcohol (by the short chain
CC dehydrogenases dmxR12 or dmxR8) and hydroxylated at C-5 by dmxR9,
CC yielding the electron-rich aromatic which could eliminate H(2)O to form
CC the ortho-quinonemethide, followed by tautomerisation to paraquinone
CC and complete the formal reduction to produce the 10-methylgroup
CC (Probable). Conjugate addition of C-4a-OH to the resulting paraquinone
CC by the monooxygenase dmxR10 then gives cyclohexadienone, which is then
CC reduced at C-5 by the short chain dehydrogenase dmxR3 to give the
CC dihydroxanthone (Probable). The 6,7-epoxide in the cryptosporioptides
CC could be introduced by the cytochrome P450 monooxygenase dmxL3
CC (Probable). The highly reducing PKS dmxL2 manufactures butyrate, which
CC is further carboxylated by dmxL1 to form ethylmalonate
CC (PubMed:30996871). It is not yet clear whether the carboxylation occurs
CC while the butyrate is attached to the ACP of dmxL2, but this unusual
CC fungal metabolite could then be esterified to O-5 by the O-
CC acetyltransferase dmxR13 (PubMed:30996871). Finally, dimerization
CC performed by dmxR5 gives the observed dimers cryptosporioptides A, B
CC and C as the final products of the pathway (PubMed:30996871).
CC {ECO:0000269|PubMed:30996871, 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; QCL09099.1; -; Genomic_DNA.
DR SMR; A0A4P8DJW5; -.
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 PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW NAD; NADP; Oxidoreductase.
FT CHAIN 1..324
FT /note="Short chain dehydrogenase/reductase dmxR8"
FT /id="PRO_0000453447"
FT ACT_SITE 200
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 25..33
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 52..53
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 82..84
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 229..231
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 324 AA; 35296 MW; E4D8BC7D9FFFB670 CRC64;
MGFLYSQLFK SLPYPTGNYS GKTIVITGSN VGLGKEAARH YVRLGASKMI LAVRSLDKGH
DAKHDIEGTT KCADNVIEVW KLDMASYDSV QKFAARVVTE LPRVDIFIAN AGIAPGSYRT
AEDNESSITV NVVSTFLLAA LVMPKMKSTA ATFKTRPTFT ITSSDVHGHT TFPQKSAPDG
QIIATVNDKA TAEKIWDDMY PISKLLEVLG VRSIAEQNPA SKFPVTINCV NPGLCHSELG
RDFPTIGFWL IKFFLARTTE VGSRTLVHAG SQGEDSHGQY MSDCEIGTPA PFVTSVEGKE
TQDRVWNELV KKLDAIKPGV TSNF
