FFSJ_ASPFV
ID FFSJ_ASPFV Reviewed; 614 AA.
AC A0A7L8UYL4;
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=FAD-linked oxidoreductase ffsJ {ECO:0000303|PubMed:32913332};
DE EC=1.-.-.- {ECO:0000305|PubMed:32913332};
DE AltName: Full=Cytochalasans biosynthesis cluster protein ffsJ {ECO:0000303|PubMed:32913332};
DE Flags: Precursor;
GN Name=ffsJ {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: FAD-linked oxidoreductase; part of the gene cluster that
CC 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:Q0V6Q5,
CC ECO:0000269|PubMed:32913332, ECO:0000305|PubMed:32913332}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32913332}.
CC -!- SIMILARITY: Belongs to the oxygen-dependent FAD-linked oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; MT586757; QOG08949.1; -; Genomic_DNA.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.465.10; -; 2.
DR InterPro; IPR012951; BBE.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR Pfam; PF08031; BBE; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..614
FT /note="FAD-linked oxidoreductase ffsJ"
FT /id="PRO_5029887681"
FT DOMAIN 119..301
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT REGION 453..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 30
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 465
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 614 AA; 65433 MW; 2F3838534C867FE5 CRC64;
MRLTRALTPA ILALPAAHAA ASLQDWQSLN TTLDHRLHAV TPLALPCFSI YNNHSHAPNE
DACLNIQDHY TNASYRVDQV SAYVFSQSET CSPIPSQQCE LDPSDPSNPA AYTNISCNTG
SLPAYYIDVQ HASDVTAAFH FAAKTNTAIS IKNSGHDYNG RSSGPGSLSL RTRTLRSTTY
HPSFTPASCK TPTGKAVTLG AGVNFHEVYT FAHENKVTFV GGSGPTVGAS GGWVLTGGHG
VLSRAYGLGI DRVVEFELVT PDGEHRIANA CQNADLFWAL RGGGGSTFGV VLSSTHRVEP
EAPLSLAYLA LPPNASSSTS AAFLDLLVNY TLPWAEDAWG GFGNAAATIL ATPLLSLPEA
KTSMATAIDF VTAHGGTGYV ETLSSFYEMY TKYIVPSASA VGSVRFNHNW IIPNSLFATA
SGQKKLRKHL DWMGSVGLVP GLLETTPYLY SGNGHGRSNN NNSNNSSTST STSTSSKNGS
VKPYAYGGKE TTSSTPAWRN SAAVLIAEVG WAFNATLSEK KALAKTLVEA SERVRELAPG
SGAYANEAHP WVEDWQDAFW GGNYRRLADL KKKWDPKGLL GCWHCVGSEG EGKKETGTAW
RAEVVGGKCL GRLI
