FLVD_ASPFN
ID FLVD_ASPFN Reviewed; 511 AA.
AC B8NHD9;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Cytochrome P450 monooxygenase flvD {ECO:0000303|PubMed:31885262};
DE EC=1.-.-.- {ECO:0000269|PubMed:31885262};
DE AltName: Full=Flavunoidine biosynthesis cluster protein D {ECO:0000303|PubMed:31885262};
GN Name=flvD {ECO:0000303|PubMed:31885262}; ORFNames=AFLA_135440;
OS Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS / JCM 12722 / SRRC 167).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=332952;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RX PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT aflatoxin contamination of food and feed.";
RL Genome Announc. 3:E0016815-E0016815(2015).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31885262; DOI=10.1021/jacs.9b13046;
RA Yee D.A., Kakule T.B., Cheng W., Chen M., Chong C.T.Y., Hai Y., Hang L.F.,
RA Hung Y.S., Liu N., Ohashi M., Okorafor I.C., Song Y., Tang M., Zhang Z.,
RA Tang Y.;
RT "Genome mining of alkaloidal terpenoids from a hybrid terpene and
RT nonribosomal peptide biosynthetic pathway.";
RL J. Am. Chem. Soc. 142:710-714(2020).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of flavunoidine, an alkaloidal terpenoid with
CC a tetracyclic cage-like core connected to dimethylcadaverine via a C-N
CC bond and acylated with 5,5-dimethyl-L-pipecolate (PubMed:31885262). The
CC tetracyclic core is synthesized by the terpene cyclase flvE and the
CC cytochrome P450 monooxygenase flvD (PubMed:31885262). The terpene
CC cyclase flvE catalyzes the cyclization of farnesyl pyrophosphate (FPP)
CC to form (1R,4R,5S)-(+)-acoradiene and the cytochrome P450 monooxygenase
CC flvD is then responsible for oxidative conversion of (1R,4R,5S)-(+)-
CC acoradiene into the tetracyclic cage present in the final product
CC flavunoidine (PubMed:31885262). The cytochrome monooxygenase flvC then
CC hydroxylates the C-10 position (PubMed:31885262). The second terpene
CC cyclase flvF is required for attachment of the C-7 axial
CC dimethylcadaverine which is itself produced by the N-methyltransferase
CC flvH and the decarboxylase flvG via methylation of L-lysine to give
CC N,N-dimethyl-L-Lysine, and decarboxylation to afford
CC dimethylcadaverine, respectively (PubMed:31885262). The NRPS flvI
CC acylates the terpenoid core at the hydroxylated C-10 with
CC dimethylpipecolate to yield final flavunoidine (PubMed:31885262). The
CC bifunctional enzyme flvA and the dehydrogenase flvB are responsible for
CC the synthesis of the dimethylpipecolate precursor (PubMed:31885262).
CC The PLP-dependent lyase domain of flvA might use L-O-acetyl-homoserine
CC and alpha-keto-isovalerate to form an intermediary ketone that can
CC cyclize intramolecularly to yield an imine (PubMed:31885262). The imine
CC can be reduced by flvB to yield the 6-carboxylated pipecolate
CC (PubMed:31885262). The C-terminal alpha-KG-dependent oxygenase domain
CC of flvA is then proposed to catalyze the decarboxylation to yield
CC dimethylpipecolate (PubMed:31885262). {ECO:0000269|PubMed:31885262}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31885262}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; EQ963478; EED50781.1; -; Genomic_DNA.
DR RefSeq; XP_002379557.1; XM_002379516.1.
DR EnsemblFungi; EED50781; EED50781; AFLA_135440.
DR VEuPathDB; FungiDB:AFLA_135440; -.
DR eggNOG; KOG0158; Eukaryota.
DR HOGENOM; CLU_001570_14_4_1; -.
DR OMA; GPYLEFY; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..511
FT /note="Cytochrome P450 monooxygenase flvD"
FT /id="PRO_0000454480"
FT TRANSMEM 13..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 451
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 511 AA; 57584 MW; 2E7127289960739A CRC64;
MLDTISESRP NGLATLGVVV ATFATYLALK ALYNLYLHPL RKFPGPKLAA IGPYYEFYYD
VMKDGMFLWE MERMHQVYGP IVRVNANEIH IRDPHYYSTV YAGNHRSTDK YHDAVAAFSV
PQASLATIHH KVHRLRRSIL NPYFSKAAVT RLESAINERI ERMCSRLEET MHYGQVVDLD
AGFAALTADI VTTYFYGQNF DYLGNEGFKF QVRDAILGLI QFYHFTRFFP WIANTIKKLP
IPIMRLIHPG AAYLVSSQEE IKDSIRASLD KGNKADAKSV IVQALEDPTI PPQERTLDRL
GDEGTTIIFA GTETTARALS VGMFHILNNK TILKKLREEL DTLPGVSSGV YSHVQLECLP
YLTGAVQESL RLSHGPAIRL PRVANDKALK YGDYIIPPGT PVSLCTVLVH QDPCIFPDPH
RFDPERWVKA SKEGVNLDKF IAAFTKGTRQ CLGINLAYAE IYLTFAKLIR TFNMEIYDTT
VDDLTVHHIR LTGAPKQGTG EVKVKVTEKI L
