FLVG_ASPFN
ID FLVG_ASPFN Reviewed; 425 AA.
AC B8NHE2;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Decarboxylase flvG {ECO:0000303|PubMed:31885262};
DE EC=4.1.1.- {ECO:0000269|PubMed:31885262};
DE AltName: Full=Flavunoidine biosynthesis cluster protein G {ECO:0000303|PubMed:31885262};
GN Name=flvG {ECO:0000303|PubMed:31885262}; ORFNames=AFLA_135470;
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: Decarboxylase; 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=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P11926};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31885262}.
CC -!- SUBUNIT: Homodimer (By similarity). Only the dimer is catalytically
CC active, as the active sites are constructed of residues from both
CC monomers (By similarity). {ECO:0000250|UniProtKB:P11926}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P08432}.
CC -!- SIMILARITY: Belongs to the Orn/Lys/Arg decarboxylase class-II family.
CC {ECO:0000305}.
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DR EMBL; EQ963478; EED50784.1; -; Genomic_DNA.
DR RefSeq; XP_002379560.1; XM_002379519.1.
DR STRING; 5059.CADAFLAP00007425; -.
DR EnsemblFungi; EED50784; EED50784; AFLA_135470.
DR VEuPathDB; FungiDB:AFLA_135470; -.
DR eggNOG; KOG0622; Eukaryota.
DR HOGENOM; CLU_026444_1_2_1; -.
DR OMA; CPEQPWH; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016831; F:carboxy-lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0006596; P:polyamine biosynthetic process; IEA:InterPro.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 2.40.37.10; -; 1.
DR Gene3D; 3.20.20.10; -; 1.
DR InterPro; IPR009006; Ala_racemase/Decarboxylase_C.
DR InterPro; IPR022643; De-COase2_C.
DR InterPro; IPR022644; De-COase2_N.
DR InterPro; IPR000183; Orn/DAP/Arg_de-COase.
DR InterPro; IPR002433; Orn_de-COase.
DR InterPro; IPR029066; PLP-binding_barrel.
DR PANTHER; PTHR11482; PTHR11482; 1.
DR Pfam; PF02784; Orn_Arg_deC_N; 1.
DR Pfam; PF00278; Orn_DAP_Arg_deC; 1.
DR PRINTS; PR01179; ODADCRBXLASE.
DR PRINTS; PR01182; ORNDCRBXLASE.
DR SUPFAM; SSF50621; SSF50621; 1.
DR SUPFAM; SSF51419; SSF51419; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Decarboxylase; Lyase; Pyridoxal phosphate.
FT CHAIN 1..425
FT /note="Decarboxylase flvG"
FT /id="PRO_0000454483"
FT ACT_SITE 365
FT /note="Proton donor; shared with dimeric partner"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 213
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 250
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 281..284
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT BINDING 331..332
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P07805"
FT BINDING 366
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P07805"
FT BINDING 395
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P11926"
FT SITE 210
FT /note="Stacks against the aromatic ring of pyridoxal
FT phosphate and stabilizes reaction intermediates"
FT /evidence="ECO:0000250|UniProtKB:P00860"
FT MOD_RES 82
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P11926"
SQ SEQUENCE 425 AA; 46911 MW; BC940FAB9D17D1AF CRC64;
MPYATEETSS VAWFPEGNLC HSKTCGPRTN GIVLEAMKGK LSQPSEWDRS EPFCVMDLGY
VYNEYQRWTS LLPDVKPFYA VKCNPDTHII KVLNAMNSGF DCASRNEMEL VMSQGVAPER
IIFANPCKKI SDLEYAQQSG VRKMTFDNEA ELQKIRQRFP DAQLILRCLA SDPSATYSLG
SKFGASSATS VKLLQCAKSW GLSVVGVSFH IGSNAKDPTA FDKAIQNSRE VFDAGLRTGH
DMHLLDIGGG FSAHNFDAMA SSIRQCIGKY FCGIDVEIVA EPGRYFAAGA LTLACGIIGR
RDAAANDEDK ENRHMLYLND GVYGTFICNI FEPGPQPKVL RASGDFYPLD SEDEYERYTI
WGPTCDGTDC VAESVALPKS LAIDDWLYFP EMGAYSTCLS TGFNGFHSDR ETIYMSSDPA
ADIYL
