ID   LUC6_FUSSX              Reviewed;         419 AA.
AC   A0A6J4B4M6;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   07-OCT-2020, sequence version 1.
DT   03-AUG-2022, entry version 4.
DE   RecName: Full=Hydrolase LUC6 {ECO:0000303|PubMed:32043422};
DE            EC=3.7.1.- {ECO:0000250|UniProtKB:S0EE80};
DE   AltName: Full=Lucilactaene biosynthesis cluster protein 6 {ECO:0000303|PubMed:32043422};
GN   Name=LUC6 {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: Hydrolase; part of the gene cluster that mediates the
CC       biosynthesis of the mycotoxin lucilactaene and the lucilactaene-related
CC       compound NG-391 that act as cell cycle inhibitors with potent growth
CC       inhibitory activity against malarial parasites, moderate growth
CC       inhibitory activity against cancer cells, and no activity against
CC       bacteria and fungi (PubMed:32043422). Within the cluster, LUC5, LUC6,
CC       LUC2 and LUC1 are sufficient for lucilactaene production (By
CC       similarity). The roles of the other LUC members are yet undetermined
CC       (By similarity). The hybrid PKS-NRPS synthetase LUC5 is responsible for
CC       the condensation of one acetyl-coenzyme A (CoA) unit with six malonyl-
CC       CoA units and the amide linkage of the arising heptaketide and
CC       homoserine, subsequently releasing the first intermediate, as an
CC       alcohol with an open ring structure (By similarity). Lucilactaene and
CC       NG-391 lack the 7-methyl group present in fusarins which is inserted in
CC       fusarins by the C-methyltransferase (CMeT) domain of the fusarin
CC       synthetase FUS1, suggesting that the CMet domain of LUC5 does not
CC       methylate this position (Probable). The cytochrome P450 monooxygenase
CC       LUC2 participates in multiple oxidation processes at carbon C-20 and is
CC       able to use the LUC5 product as substrate (By similarity). This
CC       reaction seems to be essential before the 2-pyrrolidone ring closure
CC       can be catalyzed by LUC6 (By similarity). LUC2 is able to further
CC       oxidizes carbon C-20 after ring closure, resulting in the formation of
CC       demethyllucilactaene (By similarity). As the last step, the
CC       methyltransferase LUC1 methylates the hydroxyl group at C-21 to
CC       generate lucilactaene (PubMed:32043422). {ECO:0000250|UniProtKB:S0EE80,
CC       ECO:0000269|PubMed:32043422, ECO:0000305|PubMed:32043422}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000250|UniProtKB:S0EE80}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. FUS2 hydrolase
CC       family. {ECO:0000305}.
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DR   EMBL; LC515193; BBQ09586.1; -; Genomic_DNA.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR010520; FrsA-like.
DR   Pfam; PF06500; FrsA-like; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   3: Inferred from homology;
KW   Hydrolase.
FT   CHAIN           1..419
FT                   /note="Hydrolase LUC6"
FT                   /id="PRO_0000454639"
FT   ACT_SITE        238
FT                   /evidence="ECO:0000250|UniProtKB:Q93NG6"
SQ   SEQUENCE   419 AA;  46287 MW;  4E66429F91314F4D CRC64;
     MHQIFPSTFF NFEFLRLLGT APYLGAETGE CLATAARIKD GDPESWYQAW YEQAQKALAL
     ADEAKAVGDG PGAAWGYIRA SNYFRASEFL LHCTPEDPRI LSSAVASADA FDKGWILLDG
     SVRKVEIPYE GGNTLPGRLY LPAPHHQVSG KIPVVVQTGG FDSTQEELYY YGAAGALPRG
     YAVFSFDGPG QGLSLRKDKL YLRPDWEHVT SKVLDHVIGE LAPVHNLDVD RLAVFGASLG
     GYLSLRAAAD PRVKAVVSCD GPLDLFDITR SRMPPWFING WLSGWLSDGF FNWVIDRLAS
     VNFQLAWEFG HSKWVYGVKT PADVMRTMQK FSLKDGYLSK IKCPTLITGA ADSFYFTPQQ
     NAHPIFDSLS ALGPAEKHLW IGKDVEGGGL QAKIGALALM HHKMFAWLDE TFGIRRDEL