DMXL3_CRYX8
ID DMXL3_CRYX8 Reviewed; 514 AA.
AC A0A4P8DJE5;
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=Cytochrome P450 monooxygenase dmxL3 {ECO:0000303|PubMed:30996871};
DE EC=1.-.-.- {ECO:0000305|PubMed:30996871};
DE AltName: Full=Dimeric xanthone biosynthesis cluster protein L3 {ECO:0000303|PubMed:30996871};
GN Name=dmxL3 {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: 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:0000305|PubMed:30996871}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MK182094; QCL09088.1; -; Genomic_DNA.
DR SMR; A0A4P8DJE5; -.
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:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002974; Cyt_P450_E_CYP52.
DR InterPro; IPR002402; Cyt_P450_E_grp-II.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00464; EP450II.
DR PRINTS; PR01239; EP450IICYP52.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..514
FT /note="Cytochrome P450 monooxygenase dmxL3"
FT /id="PRO_0000453475"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 459
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"
SQ SEQUENCE 514 AA; 58013 MW; AC89C11F1C5D0848 CRC64;
MALYLQIVGI IGGLYLVSTA FKILSRYSRS WKAARQHGCK PVKRYPNREP FLGSDLSRIL
KEENKRGKGL EAYANLHRTY GDTFAFKALS PTQLSTCDPK NIQTIATTNF DHWGVEPMRG
DTLAPFLGPG VLTHDGQIWK RARANIRPTF NRAEVADLEN FELYVSSLLG LIPRDGRTVD
LAPLFKKLFL DTATEFIFGR SVGSLVPDSP FNALEFMKAF DASAIGLALR IKAGALKPLL
FCFDKTWEKS YTQVHNFVDN QVRKALQPHS DLEKTEKLGH DSEQREKFIL LDQMTKETRD
PLVLRDQVLN VFMPARGVSA TAISNIIFEL ARHPDSWESL QREVQSINGQ PLTFDLIRSL
KVAKTIVYET LRIHPPAPMI KRVALRDTIL PTGGGPDQLS PVFVPKGTII SVHIYSVQTD
PKIWGDDAKE FKPQRWAEGK PLWESKWQYE PFFAGPRMCP GQQMVLTQVT YLLVRLAQEF
KGLENRDEVN EYLALGELTV QSKNGAKVSL TPAR
