ID   FFSI_ASPFV              Reviewed;         340 AA.
AC   A0A7L8UXK7;
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=Short-chain dehydrogenase/reductase ffsI {ECO:0000303|PubMed:32913332};
DE            EC=1.1.1.- {ECO:0000305|PubMed:32913332};
DE   AltName: Full=Cytochalasans biosynthesis cluster protein ffsI {ECO:0000303|PubMed:32913332};
GN   Name=ffsI {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: Short-chain dehydrogenase/reductase; part of the gene cluster
CC       that mediates the biosynthesis of the cytotoxic leucine-containing
CC       cytochalasans, including aspochalasin C, aspochalasin E, TMC-169,
CC       flavichalasine F, aspergillin PZ, aspochalasin M and flavichalasine G
CC       (PubMed:32913332). The first step in the pathway is catalyzed by the
CC       hybrid PKS-NRPS ffsA that utilizes 8 units of malonyl-CoA to
CC       iteratively assemble the octaketide chain before addition of L-leucine
CC       by the C-terminal NRPS modules (PubMed:32913332). Because ffsA lacks a
CC       designated enoylreductase (ER) domain, the required activity is
CC       provided the enoyl reductase fssC (Probable). The methyltransferase
CC       (MT) domain of ffsA catalyzes the alpha-methylation at C10 and C14
CC       using S-adenosyl-L-methionine as the methyl-donating cosubstrate
CC       (Probable). Reduction by the hydrolyase ffsE, followed by dehydration
CC       and intra-molecular Diels-Alder cyclization by the Diels-Alderase ffsF
CC       then yield the required isoindolone-fused macrocycle (By similarity). A
CC       number of oxidative steps catalyzed by the tailoring cytochrome P450
CC       monooxygenase ffsD, the FAD-linked oxidoreductase ffsJ and the short-
CC       chain dehydrogenase/reductase ffsI, are further required to afford the
CC       final products (Probable). {ECO:0000250|UniProtKB:Q0V6Q2,
CC       ECO:0000269|PubMed:32913332, ECO:0000305|PubMed:32913332}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32913332}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; MT586757; QOG08946.1; -; Genomic_DNA.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   NAD; NADP; Oxidoreductase.
FT   CHAIN           1..340
FT                   /note="Short-chain dehydrogenase/reductase ffsI"
FT                   /id="PRO_0000454529"
FT   ACT_SITE        211
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   BINDING         38..46
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         65..66
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         95..97
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         238..240
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
SQ   SEQUENCE   340 AA;  36300 MW;  364EF28C48EB5F4C CRC64;
     MAEAITSVPA KSSLSAFWWA SKHPPADPTT SFAGKTILIT GPNAGLGYEA ALKFAALGAS
     QLIFGVRSLA RGKEAKASIE AKTKCAPSVI HLLQLDMASY ASIESFAREV NSKFPVVHAA
     VLNAGVAPPA YKRSPEGWEM ALQVNVISTA YLAILLLPKL RATGIAAGEP THLEFVTSVG
     HGDVAVETVR DARSILGKVN EEANFKFTAQ YSITKLLEMW VMRHVAAAAR SSEVIVNGAC
     PSLCKSSLGR DFSIMLRAPD SLMKAIIGRT AEQGSRILVS AVTTGQKAHG GFWSHDRIAV
     PGVLVTSDEG KKLSEQFWKE ILDELSKQNP DVEKLLSESS