MILC_CORMM
ID MILC_CORMM Reviewed; 526 AA.
AC G3JUI6;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Cytochrome P450 monooxygenase milC {ECO:0000303|PubMed:34548637};
DE EC=1.-.-.- {ECO:0000269|PubMed:34548637};
DE AltName: Full=Cordypyrones biosynthesis cluster protein C {ECO:0000303|PubMed:34548637};
GN Name=milC {ECO:0000303|PubMed:34548637}; ORFNames=CCM_09344;
OS Cordyceps militaris (strain CM01) (Caterpillar fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Cordycipitaceae; Cordyceps.
OX NCBI_TaxID=983644;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CM01;
RX PubMed=22112802; DOI=10.1186/gb-2011-12-11-r116;
RA Zheng P., Xia Y., Xiao G., Xiong C., Hu X., Zhang S., Zheng H., Huang Y.,
RA Zhou Y., Wang S., Zhao G.-P., Liu X., St Leger R.J., Wang C.;
RT "Genome sequence of the insect pathogenic fungus Cordyceps militaris, a
RT valued traditional Chinese medicine.";
RL Genome Biol. 12:RESEARCH116.1-RESEARCH116.21(2011).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=34548637; DOI=10.1038/s41429-021-00478-3;
RA Gao Y.L., Yu C., Li L.;
RT "Heterologous expression of a natural product biosynthetic gene cluster
RT from Cordyceps militaris.";
RL J. Antibiot. 75:16-20(2022).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of cordypyrones A and B, 2 pyrones that show
CC modest activities against pathogenic bacteria including methicillin-
CC resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis and
CC Bacillus cereus (PubMed:34548637). The HR-PKS milA catalyzes the
CC formation of cordypyrones A via condensation of one acetate with 10
CC malonate units (PubMed:34548637). Since milA lacks an enoyl reductase
CC domain, the 2 beta-keto processing domains DH and KR of milA
CC collaborate with the trans-enoyl reductase milB to catalyze the
CC different levels of reduction (PubMed:34548637). The cytochrome P450
CC monooxygenase milC then hydroxylates the C-22 of cordypyrones A to
CC yield cordypyrones B (PubMed:34548637). {ECO:0000269|PubMed:34548637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cordypyrone A + O2 + reduced [NADPH--hemoprotein reductase] =
CC cordypyrone B + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:71079, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:190187,
CC ChEBI:CHEBI:190188; Evidence={ECO:0000269|PubMed:34548637};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71080;
CC Evidence={ECO:0000269|PubMed:34548637};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:22112802}.
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; JH126407; EGX87722.1; -; Genomic_DNA.
DR RefSeq; XP_006674541.1; XM_006674478.1.
DR STRING; 983644.G3JUI6; -.
DR EnsemblFungi; EGX87722; EGX87722; CCM_09344.
DR GeneID; 18171347; -.
DR KEGG; cmt:CCM_09344; -.
DR eggNOG; KOG0157; Eukaryota.
DR HOGENOM; CLU_001570_27_0_1; -.
DR InParanoid; G3JUI6; -.
DR OMA; QIVTHRG; -.
DR OrthoDB; 1247045at2759; -.
DR Proteomes; UP000001610; Unassembled WGS sequence.
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; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
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 Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..526
FT /note="Cytochrome P450 monooxygenase milC"
FT /id="PRO_0000455747"
FT TRANSMEM 2..20
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 470
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 526 AA; 57878 MW; 0AF0394F98D29520 CRC64;
MAIHAAYIFI AATLIALYVA RRMREQHARQ KLARDQGCEP LTTAINKLPY GLDRKWQIVT
HRGNILDDLI TTRFAELGCY IYTDNQWGSP PIICAEPATM KAVLSTKFRD WDMDSNRYPA
LGPWLGRGVL VSSHQGKGSL WATARALLRP MFANTATYNH ALIEPSVQEF LSILGHLNQA
GAPDKDLLPF IRRLNVDIIT TVFCGGSINE QQSGLAIAVG ADAKHRKPVL EEAFDTIEPI
AGLRLQTGSM YWLFTSKPFR DGCETFTGLA DGWINRALSK RDEKPDLSQD EGAAAREKNF
TEELVSSTDD RELLRDILVQ LLFAGIDTST SMLSFALVEL GRHPSAWARL RAELAAHNML
SGGPETITAA QLKECAFLQN IIKETLRLYP PVPINSREAI RDTVLPSGGG ADGSKPVFVP
KGTSLKYSPY VMHRREDLYG PDALLWNPDR WIGRAPGWDY LPFNGGPRVC IGQKFALSSS
AYVLARLAQQ FDTCTALPTT GPIDSKLGAV LVPKAGVPVS LTNSTT
