FLVE_ASPFN
ID FLVE_ASPFN Reviewed; 390 AA.
AC B8NHE0;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Terpene cyclase flvE {ECO:0000303|PubMed:31885262};
DE EC=4.2.3.- {ECO:0000269|PubMed:31885262};
DE AltName: Full=Flavunoidine biosynthesis cluster protein E {ECO:0000303|PubMed:31885262};
GN Name=flvE {ECO:0000303|PubMed:31885262};
GN ORFNames=AFLA_135450, G4B84_005464;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC 167;
RA Fountain J.C., Clevenger J.P., Nadon B., Youngblood R.C., Korani W.,
RA Chang P.-K., Starr D., Wang H., Isett B., Johnston H.R., Wiggins R.,
RA Chu Y., Agarwal G., Kemerait R.C., Pandey M.K., Bhatnagar D.,
RA Ozias-Akins P., Varshney R.K., Scheffler B.E., Vaughn J.N., Guo B.;
RT "Two new chromosome-level Aspergillus flavus reference genomes reveal a
RT large insertion potentially contributing to isolate stress tolerance and
RT aflatoxin production.";
RL Submitted (JUL-2020) to the EMBL/GenBank/DDBJ databases.
RN [3]
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:P13513};
CC Note=Some of the cofactor binding sites show unusual localization
CC within the protein. {ECO:0000250|UniProtKB:P13513};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31885262}.
CC -!- DOMAIN: The conserved active-site motif D(D/E)XX(D/E) is required for
CC coordinating the divalent metal ions that stabilize the PPI moiety of
CC the substrate. {ECO:0000250|UniProtKB:Q9UR08}.
CC -!- SIMILARITY: Belongs to the trichodiene synthase family. {ECO:0000305}.
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DR EMBL; EQ963478; EED50782.1; -; Genomic_DNA.
DR EMBL; CP059868; QMW30129.1; -; Genomic_DNA.
DR RefSeq; XP_002379558.1; XM_002379517.1.
DR STRING; 5059.CADAFLAP00007423; -.
DR EnsemblFungi; EED50782; EED50782; AFLA_135450.
DR VEuPathDB; FungiDB:AFLA_135450; -.
DR eggNOG; ENOG502SQ3X; Eukaryota.
DR HOGENOM; CLU_733855_0_0_1; -.
DR OMA; FEGCWIE; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0045482; F:trichodiene synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0016106; P:sesquiterpenoid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR010458; TRI5_ascomyc.
DR InterPro; IPR024652; Trichodiene_synth.
DR Pfam; PF06330; TRI5; 1.
DR PIRSF; PIRSF001388; TRI5; 1.
DR SFLD; SFLDG01021; Trichodiene_Synthase_Like; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Lyase; Magnesium; Metal-binding.
FT CHAIN 1..390
FT /note="Terpene cyclase flvE"
FT /id="PRO_0000454481"
FT MOTIF 102..106
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 102
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13513"
FT BINDING 166
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13513"
FT BINDING 227
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13513"
FT BINDING 231
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13513"
FT BINDING 235
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13513"
FT BINDING 241
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P13513"
FT BINDING 243
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P13513"
SQ SEQUENCE 390 AA; 44707 MW; 8A493E00B4AD5507 CRC64;
MPGKQFPLKE YIAALAKFLD TIEYQDDNFS HEQRVESLRY VYQHTAKHFD QPIEKAAVTV
SPKRLQAVMR TSTLVTVYCW VKCPLDVMVG VSIYFAYIIM LDDSSDTPTT EMKTFCEDLI
KGRPQKHLFW QRMNAHLTNF LRYYDGFCAI TIFRSTLDFF QGCWIEQNNF GGFPGSSYFP
HFLRRLNGLG GISSATLFPR SEFDEGTVFE EIVTAIAQIE PQLTLCNDLI SFYKEYDSPR
DQINLVSNLA HCNGVSWEIA FEELTRDTIL YCEQLVTVFK GKDPKVEATV RAFVHGYVTW
HLCDPRFRMQ EVYEQAGQSE ADLKFRHFYE QATSIGVIDF KLWASPSRLS SDKRKHEQAF
GDDPQNGKTR VLESIGQANA SEAVALAPLA
