ID   FFSC_ASPFV              Reviewed;         367 AA.
AC   A0A7L8UWS6;
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=Trans-enoyl reductase ffsC {ECO:0000303|PubMed:32913332};
DE            EC=1.-.-.- {ECO:0000305|PubMed:32913332};
DE   AltName: Full=Cytochalasans biosynthesis cluster protein ffsC {ECO:0000303|PubMed:32913332};
GN   Name=ffsC {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: Trans-enoyl reductase; part of the gene cluster that mediates
CC       the 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:Q0V6Q3,
CC       ECO:0000269|PubMed:32913332, ECO:0000305|PubMed:32913332}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32913332}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC   -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC       family. {ECO:0000305}.
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DR   EMBL; MT586757; QOG08941.1; -; Genomic_DNA.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   GO; GO:0019166; F:trans-2-enoyl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR   InterPro; IPR013154; ADH_N.
DR   InterPro; IPR011032; GroES-like_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020843; PKS_ER.
DR   Pfam; PF08240; ADH_N; 1.
DR   SMART; SM00829; PKS_ER; 1.
DR   SUPFAM; SSF50129; SSF50129; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   NADP; Nucleotide-binding; Oxidoreductase.
FT   CHAIN           1..367
FT                   /note="Trans-enoyl reductase ffsC"
FT                   /id="PRO_0000454525"
FT   BINDING         55..58
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         143..150
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255"
FT   BINDING         203..206
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         221
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         268..269
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         288..292
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255"
FT   BINDING         357..358
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ   SEQUENCE   367 AA;  39437 MW;  97D2C80F3D36CF07 CRC64;
     MSPARTLESS PLPTTQTAII QGEGGILSIH HNAPLPTLRP DRILVKVAYV AINPCDWKMA
     DRFPTPGCVD GCDFSGTVVA LGSDWAKTGR FKIGDRVCGG VHGSNPIDQS TGCFADYVSA
     DAQFTFHVPE YMGMEDAAAV GGTGIGTLGL ALKRSLGLPG SPRDPVPESE SVQVLVYAAS
     TSVGTLATQL LRMSGHKPIG VCSAKNFDMV KSYGAVKLFD YHSPTCAQDI RAYTKNTLAH
     ILDPITEPKT TELCYAAMGR AGGKYCALEA FAEEFCTRRV VKPELVMGMA ILGGRIALDY
     GYESEADPEK RVFGVSWYEE MQELLDSGRL RNHPVRSFPG GFEGIMKGLH LLKTKQVSGE
     KLIVQLG