DMXR5_CRYX8
ID DMXR5_CRYX8 Reviewed; 508 AA.
AC A0A4P8DJC8;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Cytochrome P450 monooxygenase dmxR5 {ECO:0000303|PubMed:30996871};
DE EC=1.14.13.- {ECO:0000305|PubMed:30996871};
DE AltName: Full=Dimeric xanthone biosynthesis cluster protein R5 {ECO:0000303|PubMed:30996871};
GN Name=dmxR5 {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, DISRUPTION PHENOTYPE, AND
RP 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: Cytochrome P450 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=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30996871}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Abolished dimer production and leads to the
CC accumulation of the monomer intermediate hemi-cryptosporioptide.
CC {ECO:0000269|PubMed:30996871}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MK182094; QCL09096.1; -; Genomic_DNA.
DR SMR; A0A4P8DJC8; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 3: Inferred from homology;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..508
FT /note="Cytochrome P450 monooxygenase dmxR5"
FT /id="PRO_0000453476"
FT TRANSMEM 24..44
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 481..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 451
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 405
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 462
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 508 AA; 57514 MW; 77D5712A3778230A CRC64;
MNSTPSAPPL KMEALDLDIF QPSLTLGLGA ILVVLMSFLA FLSYTPSFDK KVPAFTTHTH
PFIGAADFMW RKNHFWRASM EESKTGTFSF WVGKKHVVGL SGEAARKTFM DSPGLDFVGG
ARIRGVSLLP NPPTPEIFRP GFHHGRSFFL RRMIDMQKTE MLKRCLPRFT SDSRGVFDEL
AKDPSGITNP AVACWHVVFA HDVILFCSEE IVDDPKAFPN LLQMIDILQG LSSFTKVFLP
WLPTMAGMTR ARRYKYMKSI FEPLVDRRMK RGAIRREDSL QLMIDNGDRR DLIIDFVIAA
VIIAPTNSRI LTGQMLNVMA AYPSWQEKAY AEIKALAKSY AKDPEAPLAD QLDSMPLEAW
EAGFPSIDLC FKELVRMWVA ISMMRRNISS RTDEFIPAGS FAIYNTTETH FSEELYPDPH
TFKPERWLEG NANVQKQAYG FVGWGEGRHP CPGKRWAKLQ LNITIAYALA KFKWTSVDKT
EHKKSTQESG HGVPLPSKLS KFSPREEN
