DMXR9_CRYX8
ID DMXR9_CRYX8 Reviewed; 517 AA.
AC A0A4P8DJF6;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=FAD-dependent monooxygenase dmxR9 {ECO:0000303|PubMed:30996871};
DE Short=FMO dmxR9 {ECO:0000303|PubMed:30996871};
DE EC=1.-.-.- {ECO:0000305|PubMed:30996871};
DE AltName: Full=Dimeric xanthone biosynthesis cluster protein R9 {ECO:0000303|PubMed:30996871};
GN Name=dmxR9 {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: FAD-dependent monooxygenase; 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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30996871}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; MK182094; QCL09100.1; -; Genomic_DNA.
DR SMR; A0A4P8DJF6; -.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..517
FT /note="FAD-dependent monooxygenase dmxR9"
FT /id="PRO_0000453480"
FT BINDING 63
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 83..84
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 365
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 375..379
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 517 AA; 57317 MW; 044E9BD5DEE65392 CRC64;
MAPSTIGTNV AGDKYEYDPE NWMAKGTSTL NNGNGTKGTL DVDLPERHPE TGINVLVVGA
GMGGLMTTLE CWRKGHNIVG ILERNDGPVY SGDIIVIQPS AVSVLRHWPD MMRDMEDEQV
NAAVSYEQHT GRHIYGPTVP SFNELEHLAS RKGPFVAPAQ IREKFYRMLL RQVAKLGFKV
QYGKRAVSYF EDIAAGKGGV VLESGEIQVA DVVVAADGLR STSEILIAGE HTPTKSSGMS
IYRTAYPREM AMKDETVRKR WADTKEIWEY WLGPGMYIGV FFSEDVVSWG FTPRDTHGGA
TESWEPDTDP EDVVKELLRV PDWDPAIAAL VRTAPKGAIV HWPLLWRNLR REWTSSGGHV
VQLGDSAHSF VPTSGNGATQ ALEDAITLAT CLQLGGAARN APLATKIYNL LRYERVSCAQ
KMSFVNSQLK TETDWDGIWA DPIKVRTRFP KWIHNHDPED YAYAKYGQAF AHLVAGADFA
NENFPPGHHF VPWSIEEVYA DIEAGKKVEA LLDGDWS
