ID   FFSD_ASPFV              Reviewed;         531 AA.
AC   A0A7L8UVC5;
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=Cytochrome P450 monooxygenase ffsD {ECO:0000303|PubMed:32913332};
DE            EC=1.-.-.- {ECO:0000305|PubMed:32913332};
DE   AltName: Full=Cytochalasans biosynthesis cluster protein ffsD {ECO:0000303|PubMed:32913332};
GN   Name=ffsD {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: Cytochrome P450 monooxygenase; 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:Q0V6Q8,
CC       ECO:0000269|PubMed:32913332, ECO:0000305|PubMed:32913332}.
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P04798};
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32913332}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; MT586757; QOG08943.1; -; Genomic_DNA.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0008152; P:metabolic process; IEA:UniProt.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   3: Inferred from homology;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..531
FT                   /note="Cytochrome P450 monooxygenase ffsD"
FT                   /id="PRO_0000454526"
FT   TRANSMEM        40..60
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         475
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P04798"
SQ   SEQUENCE   531 AA;  60196 MW;  67EEA5D68F380E02 CRC64;
     MLQDIVEQWQ IMQQALAPLR LTRWQLTKMF AAQVYRDHPV GALLGISLSV VLLLWVISVV
     TRPKKLEDVL GLPVLGGSRT LKSDFLRIIE EGKQRYPDTP YIVNASGLQY VVYPPIFFDE
     IKRLTEQEAS AQDFFHTVTY GQWTHIGAET DALWKTIAVD LARSVPVKVP SKQKDARIAF
     DKYVGYCPES KPVTIFDTMM KIVATTNACS FVGREVGTGE WPQVVQQLPM SVYFAVMTLS
     IVPRIFRPVL LPIVLIPALL VQRKMRKILA PGIRQDMEEY ERAADRKELL KPTEDGKLPF
     TQWLMARYKP GEATAHQLAT DHLLTSFEST VSTAATLYNM ILDLAVRPEL QDELRQEVEE
     IMVDGKLPAT HLKELKKMDS MMRETFRVNP FALFSLYRIT RKPIQLSSGP KLPAGTILCV
     DSHHINNSAE LFPEPAKFDP YRFLKKREEP GAENRFQFVS TGPTDPNWGD GTQACPGRFF
     ANSTLKVCLA HVLLKYNVSL REGQERPKMV SMPNGIWAPD MAAQVLFQSR D