ID   LUC2_FUSSX              Reviewed;         509 AA.
AC   A0A6J4BC30;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   07-OCT-2020, sequence version 1.
DT   03-AUG-2022, entry version 5.
DE   RecName: Full=Cytochrome P450 monooxygenase LUC2 {ECO:0000303|PubMed:32043422};
DE            EC=1.-.-.- {ECO:0000250|UniProtKB:S0EE84};
DE   AltName: Full=Lucilactaene biosynthesis cluster protein 2 {ECO:0000303|PubMed:32043422};
GN   Name=LUC2 {ECO:0000303|PubMed:32043422};
OS   Fusarium sp.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX   NCBI_TaxID=29916;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=RK97-94;
RX   PubMed=32043422; DOI=10.1080/09168451.2020.1725419;
RA   Kato S., Motoyama T., Futamura Y., Uramoto M., Nogawa T., Hayashi T.,
RA   Hirota H., Tanaka A., Takahashi-Ando N., Kamakura T., Osada H.;
RT   "Biosynthetic gene cluster identification and biological activity of
RT   lucilactaene from Fusarium sp. RK97-94.";
RL   Biosci. Biotechnol. Biochem. 84:1303-1307(2020).
CC   -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of the mycotoxin lucilactaene and the
CC       lucilactaene-related compound NG-391 that act as cell cycle inhibitors
CC       with potent growth inhibitory activity against malarial parasites,
CC       moderate growth inhibitory activity against cancer cells, and no
CC       activity against bacteria and fungi (PubMed:32043422). Within the
CC       cluster, LUC5, LUC6, LUC2 and LUC1 are sufficient for lucilactaene
CC       production (By similarity). The roles of the other LUC members are yet
CC       undetermined (By similarity). The hybrid PKS-NRPS synthetase LUC5 is
CC       responsible for the condensation of one acetyl-coenzyme A (CoA) unit
CC       with six malonyl-CoA units and the amide linkage of the arising
CC       heptaketide and homoserine, subsequently releasing the first
CC       intermediate, as an alcohol with an open ring structure (By
CC       similarity). Lucilactaene and NG-391 lack the 7-methyl group present in
CC       fusarins which is inserted in fusarins by the C-methyltransferase
CC       (CMeT) domain of the fusarin synthetase FUS1, suggesting that the CMet
CC       domain of LUC5 does not methylate this position (Probable). The
CC       cytochrome P450 monooxygenase LUC2 participates in multiple oxidation
CC       processes at carbon C-20 and is able to use the LUC5 product as
CC       substrate (By similarity). This reaction seems to be essential before
CC       the 2-pyrrolidone ring closure can be catalyzed by LUC6 (By
CC       similarity). LUC2 is able to further oxidizes carbon C-20 after ring
CC       closure, resulting in the formation of demethyllucilactaene (By
CC       similarity). As the last step, the methyltransferase LUC1 methylates
CC       the hydroxyl group at C-21 to generate lucilactaene (PubMed:32043422).
CC       {ECO:0000250|UniProtKB:S0EE84, ECO:0000269|PubMed:32043422,
CC       ECO:0000305|PubMed:32043422}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:S0EE84}.
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; LC515193; BBQ09591.1; -; Genomic_DNA.
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   3: Inferred from homology;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..509
FT                   /note="Cytochrome P450 monooxygenase LUC2"
FT                   /id="PRO_0000454634"
FT   TRANSMEM        30..50
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         456
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   509 AA;  57154 MW;  9CD9F48FF4E6BA88 CRC64;
     MVAQPSPIVG RLKLPESMPS LVSLEELTAT KVLVTFLTIV IIAPRVFTVI KNAFSPISSI
     PGPLLNKLSP WPLTIATIKG TSHHFARSLH EKYGPIVVLA PGMVAVADTK EIKRIIQTED
     WTKSEAIYGN FRQDPQRPTL LAYTDKKAYA KRKRMLSSMF GIKYIRSMEP IMMTCVEAAV
     RQLNKFCDEG TQGVAVVDMQ HLIHSLAIDI IGITTFGGSL NVVDNGSHPL PSRLKAGLRI
     AGLMQLIPWI RFIPFLPTRD PYVDRFTYDI VDGRRQELES SQHSDLLQKL VEASDDSPGS
     DFRTSDVQDE SVVMLTAGSE TTANAELFTL MMLLKNPKVM KKLVDEVDQW YPPSEPDRQT
     DCGYSQAGMV YLQACIDETM RLVPGQATGS PRETSKDDVV LGYRIPAGTT VFPNTQEGHT
     QDAHWEEPQK FVPERWLEAQ ATNVPYWPFS AGSRVCIGKH FAFQEMHLTL VTLLRKFKFE
     YVDGQDESTV FRVAQQLKAE SYRMKVSRR