ID   FFSF_ASPFV              Reviewed;         411 AA.
AC   A0A7L8UVG6;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   07-APR-2021, sequence version 1.
DT   03-AUG-2022, entry version 5.
DE   RecName: Full=Diels-Alderase ffsF {ECO:0000303|PubMed:32913332};
DE            EC=5.5.1.- {ECO:0000305|PubMed:32913332};
DE   AltName: Full=Cytochalasans biosynthesis cluster protein ffsF {ECO:0000303|PubMed:32913332};
DE   Flags: Precursor;
GN   Name=ffsF {ECO:0000303|PubMed:32913332};
OS   Aspergillus flavipes.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=41900;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=CNL-338;
RX   PubMed=32913332; DOI=10.1038/s41429-020-00368-0;
RA   Heard S.C., Wu G., Winter J.M.;
RT   "Discovery and characterization of a cytochalasan biosynthetic cluster from
RT   the marine-derived fungus Aspergillus flavipes CNL-338.";
RL   J. Antibiot. 73:803-807(2020).
CC   -!- FUNCTION: Diels-Alderase; part of the gene cluster that mediates the
CC       biosynthesis of the cytotoxic leucine-containing cytochalasans,
CC       including aspochalasin C, aspochalasin E, TMC-169, flavichalasine F,
CC       aspergillin PZ, aspochalasin M and flavichalasine G (PubMed:32913332).
CC       The first step in the pathway is catalyzed by the hybrid PKS-NRPS ffsA
CC       that utilizes 8 units of malonyl-CoA to iteratively assemble the
CC       octaketide chain before addition of L-leucine by the C-terminal NRPS
CC       modules (PubMed:32913332). Because ffsA lacks a designated
CC       enoylreductase (ER) domain, the required activity is provided the enoyl
CC       reductase fssC (Probable). The methyltransferase (MT) domain of ffsA
CC       catalyzes the alpha-methylation at C10 and C14 using S-adenosyl-L-
CC       methionine as the methyl-donating cosubstrate (Probable). Reduction by
CC       the hydrolyase ffsE, followed by dehydration and intra-molecular Diels-
CC       Alder cyclization by the Diels-Alderase ffsF then yield the required
CC       isoindolone-fused macrocycle (By similarity). A number of oxidative
CC       steps catalyzed by the tailoring cytochrome P450 monooxygenase ffsD,
CC       the FAD-linked oxidoreductase ffsJ and the short-chain
CC       dehydrogenase/reductase ffsI, are further required to afford the final
CC       products (Probable). {ECO:0000250|UniProtKB:Q0V6Q4,
CC       ECO:0000269|PubMed:32913332, ECO:0000305|PubMed:32913332}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32913332}.
CC   -!- SIMILARITY: Belongs to the Diels-Alderase family. {ECO:0000305}.
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DR   EMBL; MT586757; QOG08948.1; -; Genomic_DNA.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
PE   3: Inferred from homology;
KW   Isomerase; Signal.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   CHAIN           18..411
FT                   /note="Diels-Alderase ffsF"
FT                   /id="PRO_5029676072"
SQ   SEQUENCE   411 AA;  45809 MW;  779886E8AC4B3EF0 CRC64;
     MTQIKLLLLS LAITAQSITY DLPSQWDHQW LTQQPLGSDT TCTTSHLTAF QMSKTKDPIF
     FSTGGTDPFL SPKMLPLNST AGEQWEFDGV SPDAKMAFVF GFYRDPNYAI LGSGNLRVSV
     EMLWPNGTRF AQVDYPTDSV IEECEWGTRG VWRADEFSYS FEVSRDLQTA RVAMHTPQVT
     GVVYLDSESK PRYPDGKIYP SETSTSEALP YFHFVEPIPV AKSQVDLMIL GESYVWSDGV
     GGMERLWGAF SWFTCLQGMN VVRLHAGPYA LSLLSFTSNI KKGNEYPSIA LFENGEPVFS
     SQRTEDSDTA DYFTFTKTYD GKVTGTLRDK VTGYELELVS PGEKKHWTFI IDHESLAFEY
     ILGGGHGGSG FAGFVQGGRV GLEQFRGIAL TEALTFPKKS PLFRSQYSET S