ILIC_NEOS2
ID ILIC_NEOS2 Reviewed; 505 AA.
AC P0DO32;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 03-AUG-2022, entry version 5.
DE RecName: Full=Cytochrome P450 monooxygenase iliC {ECO:0000303|PubMed:31216742};
DE EC=1.-.-.- {ECO:0000269|PubMed:31216742};
DE AltName: Full=Ilicicolin H biosynthesis cluster protein C {ECO:0000303|PubMed:31216742};
GN Name=iliC {ECO:0000303|PubMed:31216742};
OS Neonectria sp. (strain DH2).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Neonectria;
OC unclassified Neonectria.
OX NCBI_TaxID=1735992;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RX PubMed=31216742; DOI=10.3390/molecules24122267;
RA Lin X., Yuan S., Chen S., Chen B., Xu H., Liu L., Li H., Gao Z.;
RT "Heterologous expression of ilicicolin H biosynthetic gene cluster and
RT production of a new potent antifungal reagent, ilicicolin J.";
RL Molecules 24:0-0(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:31216742). IliC
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:31216742). The biosynthesis of ilicicolin H starts with
CC formation of the tetramic acid by the hybrid PKS-NRPS synthetase iliA
CC with the partnering trans-enoyl reductase iliB since iliA lacks a
CC designated enoylreductase (ER) domain. The cytochrome P450
CC monooxygenase iliC then catalyzes the ring expansion of the tetramate
CC to the acyclic 2-pyridone. The pericyclase iliD further converts the
CC acyclic 2-pyridone into 8-epi-ilicicolin H. 8-epi-ilicicolin H might
CC then spontaneously convert to ilicicolin H since ilicicolin H is
CC produced in the absence of the epimerase iliE, in contrast to what was
CC observed for the Talaromyces variabilis ilicolin H biosynthetic pathway
CC (PubMed:31216742) (Probable). {ECO:0000269|PubMed:31216742,
CC ECO:0000305|PubMed:31216742}.
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:31216742};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64553;
CC Evidence={ECO:0000269|PubMed:31216742};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31216742}.
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 AlphaFoldDB; P0DO32; -.
DR SMR; P0DO32; -.
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 Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..505
FT /note="Cytochrome P450 monooxygenase iliC"
FT /id="PRO_0000453069"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 453
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 505 AA; 58781 MW; 3EAAFF9D9B2B1F75 CRC64;
MITNDLIAQH SLTLTIASSV LLVFLLSRLL RKDATGKAQG CRPVAKRWQW DPILGLDIVL
AQIGALKGNY YLPWLIELHS NMPKTFEINF FGKRQIYTSE PDNLKAMTAT NFHDFGIEPM
RRHTKGSMPF ADKGISTVDG KEWEFSRFLL KPFFYREVYT STDRIEPFAD HMMALIPGDG
ESFNMQSLIQ RWFLDLTTNF IFGKPMDALE NPDRARITWA MLDVLKGGRL RAQFYMMMWA
FNWTWWYKAV AEVHDFINVH IRETYKEIEE REQRIKDGKP VEPERTDLIW YMAWNLRDEE
LLRSQLCLVF VPNNDTTSIF ISNCIWHLAR HPEAWEKLRQ EVLAHGDAPL TFEALRNMKY
LQCVLNETHR LTPNNVTQIR VCLNDSVLPV GGGKNAKEPF FVRKGDVVSI TKTVMYRDPE
IWGNDAEEFK PERFDGRRVF WEFLPFGGGP RRCPAQMMVQ TEAAYMLARL ARVYRRIEAR
DPAPYTAVMR IGPSNKTGVQ IAVYK
