ICCC_TALVA
ID ICCC_TALVA Reviewed; 504 AA.
AC A0A482NAF7;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Cytochrome P450 monooxygenase iccC {ECO:0000303|PubMed:30905148};
DE EC=1.-.-.- {ECO:0000269|PubMed:30905148};
DE AltName: Full=Ilicicolin H biosynthesis cluster protein C {ECO:0000303|PubMed:30905148};
GN Name=iccC {ECO:0000303|PubMed:30905148};
OS Talaromyces variabilis (Penicillium variabile).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces.
OX NCBI_TaxID=28576;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=HXQ-H-1;
RX PubMed=30905148; DOI=10.1021/jacs.9b02204;
RA Zhang Z., Jamieson C.S., Zhao Y.L., Li D., Ohashi M., Houk K.N., Tang Y.;
RT "Enzyme-catalyzed inverse-electron demand Diels-Alder reaction in the
RT biosynthesis of antifungal ilicicolin H.";
RL J. Am. Chem. Soc. 141:5659-5663(2019).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of ilicicolin H, a 4-hydroxy-2-
CC pyridonealkaloid that has potent and broad antifungal activities by
CC inhibiting the mitochondrial respiration chain (PubMed:30905148). IccC
CC catalyzes the ring expansion of the tetramate intermediate to the
CC acyclic 2-pyridone intermediate that contains the trans bis-diene chain
CC (PubMed:30905148). The biosynthesis of ilicicolin H starts with
CC formation of the tetramic acid by the hybrid PKS-NRPS synthetase iccA
CC with the partnering trans-enoyl reductase iccB since iccA lacks a
CC designated enoylreductase (ER) domain. The cytochrome P450
CC monooxygenase iccC then catalyzes the ring expansion of the tetramate
CC to the acyclic 2-pyridone. The pericyclase iccD further converts the
CC acyclic 2-pyridone into 8-epi-ilicicolin H. Finally, the epimerase iccE
CC converts 8-epi-ilicicolin H into ilicicolin H via epimerization. IccA
CC to iccE are sufficient for ilicicolin H biosynthesis and the roles of
CC the remaining enzymes, iccF, iccG and iccH within the pathway have
CC still to be determined (PubMed:30905148) (Probable).
CC {ECO:0000269|PubMed:30905148, ECO:0000305|PubMed:30905148}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5S)-3-[(2E,4E,8S,10E,12Z)-1-hydroxy-4,8-dimethyltetradeca-
CC 2,4,10,12-tetraen-1-ylidene]-5-[(4-hydroxyphenyl)methyl]pyrrolidine-
CC 2,4-dione + O2 + reduced [NADPH--hemoprotein reductase] = 3-
CC [(2E,4E,8S,10E,12Z)-4,8-dimethyltetradeca-2,4,10,12-tetraenoyl]-4-
CC hydroxy-5-(4-hydroxyphenyl)-1,2-dihydropyridin-2-one + 2 H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:64552,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:155889, ChEBI:CHEBI:155890;
CC Evidence={ECO:0000269|PubMed:30905148};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64553;
CC Evidence={ECO:0000269|PubMed:30905148};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30905148}.
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; MK539848; QBQ83705.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A482NAF7; -.
DR SMR; A0A482NAF7; -.
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; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002974; Cyt_P450_E_CYP52.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR01239; EP450IICYP52.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..504
FT /note="Cytochrome P450 monooxygenase iccC"
FT /id="PRO_0000449002"
FT TRANSMEM 7..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 452
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 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 365
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 504 AA; 58535 MW; 6597F33113CE30AB CRC64;
MITLQNLPWI LLYTGFLAIF LSRLFSNGKQ SRDEKANGCQ PPARYPQWDP IMGLDLVYSQ
VSALKNNRYL EWLRDLHAKM PKTFSLNFFG QRWIYSIEPE ILKAVYATNF RDFGVEPIRR
HSKGSMPFAD KGVNTTDGED WEFSRLLIKP FFERNVYTDT DRIKVHADHF LSLIPADGET
FDAQPLVQRW FLDLTTEFIF GESMGSLAHP ERADIAWTML DVLRGGRLRA QMHRFMWARD
WTWWLKAVYK VHDYVNPYIR STLKELAERE ERIKQGLPVG PERTDLVWSM ATHLRDEELL
RSQLCLIIVP NNDTTSIFIS NCLWHLARHP EVWKKLREEV FALGEETPLT FEILRNMKYL
NGVLNETHRV IPNNVTQVRA CVQDTVLPVG GGPDGKWPVQ VRKGDIVSVT KTVMYRDPDY
WGSDADEFRP ERFDGLRGTW NFLPFGGGPR RCPAQMMSQT EAAYMLCRLA RTYSRIEARD
PEPYTAVMRI GPSNKTGVKI ALYK
