ID   FFSE_ASPFV              Reviewed;         450 AA.
AC   A0A7L8UVC6;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   07-APR-2021, sequence version 1.
DT   23-FEB-2022, entry version 4.
DE   RecName: Full=Hydrolase ffsE {ECO:0000303|PubMed:32913332};
DE            EC=3.7.1.- {ECO:0000305|PubMed:32913332};
DE   AltName: Full=Cytochalasans biosynthesis cluster protein ffsE {ECO:0000303|PubMed:32913332};
GN   Name=ffsE {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: Hydrolase; 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:Q0V6Q1,
CC       ECO:0000269|PubMed:32913332, ECO:0000305|PubMed:32913332}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32913332}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q93NG6}.
CC   -!- SIMILARITY: Belongs to the AB hydrolase superfamily. FUS2 hydrolase
CC       family. {ECO:0000305}.
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DR   EMBL; MT586757; QOG08947.1; -; 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; IPR000073; AB_hydrolase_1.
DR   Pfam; PF12697; Abhydrolase_6; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   3: Inferred from homology;
KW   Hydrolase.
FT   CHAIN           1..450
FT                   /note="Hydrolase ffsE"
FT                   /id="PRO_0000454527"
FT   ACT_SITE        266
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:Q4WZB3"
SQ   SEQUENCE   450 AA;  49701 MW;  217AE776053E71C0 CRC64;
     MTGPPGNPAF ATIHEFFPGN TFYNFECLRI LSTAPYGGCD PAEFLTAIAA IKPSDPETWA
     TAWSHAASQA ERIAEDALAR GDTLAARDAF LRASSYTRAS GYMRINGPTL DRHDPRALPV
     ARKTQALFRK ALPFLDCDAR IVDIPYRPTQ YSKPVSLPGY VYIPSPQNRL PDGKIPVLLN
     TGGADSVQEE LYYIHPQAGH ARGYAVITFE GPGQGIVLRE KGLYMRPDWE VVTGQVLDWL
     EGYAATLQQE EGLTLDLSRI AVVGASMGGY YALRAASDPR IKACLSIDPF YDMWDFGTRH
     ISGLFMAAWT GGWVSDATID RVIGAGMYLN FQLRWEVGVT TAFWGIESPS RILREMKRYS
     LQGGFLARVQ CPVFVSGAGK SLYFDTEEHT MRVFGDLKHL GERRRTLWMP SRPEEGGLQA
     KIGAFGLVNT KAFGFLDGVF GVKRVLEAET