FLVF_ASPFN
ID FLVF_ASPFN Reviewed; 366 AA.
AC B8NHE1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Terpene cyclase flvF {ECO:0000303|PubMed:31885262};
DE EC=4.2.3.- {ECO:0000269|PubMed:31885262};
DE AltName: Full=Flavunoidine biosynthesis cluster protein F {ECO:0000303|PubMed:31885262};
GN Name=flvF {ECO:0000303|PubMed:31885262}; ORFNames=AFLA_135460;
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: Terpene cyclase; part of the gene cluster that mediates the
CC biosynthesis of flavunoidine, an alkaloidal terpenoid with a
CC 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=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9UR08};
CC Note=Binds 3 Mg(2+) ions per monomer. {ECO:0000250|UniProtKB:Q9UR08};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31885262}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9UR08}.
CC -!- DOMAIN: The 2 conserved active-site motifs D(D/E)XX(D/E) and NSE are
CC required for coordinating the divalent metal ions that stabilize the
CC PPI moiety of the substrate. {ECO:0000250|UniProtKB:Q9UR08}.
CC -!- DOMAIN: The C-terminal WxxxxxRY motif is frequently found in terpene
CC synthases and is important to guide product formation.
CC {ECO:0000250|UniProtKB:P9WEY7}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; EQ963478; EED50783.1; -; Genomic_DNA.
DR RefSeq; XP_002379559.1; XM_002379518.1.
DR EnsemblFungi; EED50783; EED50783; AFLA_135460.
DR VEuPathDB; FungiDB:AFLA_135460; -.
DR HOGENOM; CLU_763099_0_0_1; -.
DR OMA; SMINSIP; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Lyase; Magnesium; Metal-binding.
FT CHAIN 1..366
FT /note="Terpene cyclase flvF"
FT /id="PRO_0000454482"
FT MOTIF 95..99
FT /note="D(D/E)XX(D/E) motif"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT MOTIF 225..235
FT /note="NSE motif"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT MOTIF 316..323
FT /note="WxxxxxRY motif"
FT /evidence="ECO:0000250|UniProtKB:P9WEY7"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 232
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 233
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 235
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 322..323
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
SQ SEQUENCE 366 AA; 42347 MW; 6E1C413F9E98F31B CRC64;
MEGLRRHSVM LDCKLWKDDP IYFFKTLPPY ISKYAQRADD ASIQAQIDVF GKDDVGAMPG
ALGPRGNFAA VTFAESFPDR VAMLAYLNEV LSFYECFEKQ MTEMLDATLY ANPVPKDPKY
DNPVWQANYK NTMTKWPKIL ENLDPKLGPK CVKSLVALVE GTDMEPKMAH YKTMKEYALD
RTNYIAWPVA CDNAEFGSQL NLTQDQLDSV RDIFLPLWTH SCYVYDYYHY DKEAEIHSTY
GKGRSMINSI PLLNRLKGLS VEEAKAWLKQ RCFELEKEYL QRKEDYFSEN PVEAVPVDLR
RWFLSQEDLA TGFAIWCATT YHNHPPFGEG YAAPYEKRRK EGALWFEKVT ESDQLMTGGF
EVRYAN
