DMXR1_CRYX8
ID DMXR1_CRYX8 Reviewed; 322 AA.
AC A0A4P8DJU1;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Atrochrysone carboxyl ACP thioesterase dmxR1 {ECO:0000250|UniProtKB:Q5BH31};
DE Short=ACTE dmxR1 {ECO:0000250|UniProtKB:Q5BH31};
DE EC=3.1.2.- {ECO:0000250|UniProtKB:Q5BH31};
DE AltName: Full=Dimeric xanthone biosynthesis cluster protein L {ECO:0000303|PubMed:30996871};
GN Name=dmxR1 {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: Atrochrysone carboxyl ACP thioesterase; part of the gene
CC cluster 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 -!- CATALYTIC ACTIVITY:
CC Reaction=atrochrysone carboxyl-[ACP] + H2O = atrochrysone carboxylate +
CC H(+) + holo-[ACP]; Xref=Rhea:RHEA:64236, Rhea:RHEA-COMP:9685,
CC Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:149712, ChEBI:CHEBI:149713;
CC Evidence={ECO:0000250|UniProtKB:Q5BH31};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64237;
CC Evidence={ECO:0000250|UniProtKB:Q5BH31};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q988B9};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q988B9};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30996871}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; MK182094; QCL09092.1; -; Genomic_DNA.
DR SMR; A0A4P8DJU1; -.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 3: Inferred from homology;
KW Hydrolase; Metal-binding; Zinc.
FT CHAIN 1..322
FT /note="Atrochrysone carboxyl ACP thioesterase dmxR1"
FT /id="PRO_0000453433"
FT ACT_SITE 109
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
SQ SEQUENCE 322 AA; 35278 MW; E90DDBF76CC61A66 CRC64;
MAPGKGGYKQ INKALNICAF EDYLDGQQAT LPPLQDVEQI SPRVIRVLGQ NPGKFTLQGT
NTYIVGTGSE RLIIDTGQGI PDWADLISTT LLDGNFSLSH VLLTHWHGDH TGGVPDLLRL
YPDLISGIYK HTPSKIQQPI EDGQVFKVEG ATVRAVHAPG HSSDHMCFIL EEEQAMFTGD
NVLGHGTSAV EHLSTWMAAL QQMKSHNCRK GYPAHGIVIN DLQGRITGQL AQKFRRERQV
LKALEQVKSQ ERAMAGGRGK GSVTVKQLVS TMHGDSLDGG IRELALEPFT EEILRKLAED
GKVAFEIRTG IKKWFVVGTA LD
