FLVB_ASPFN
ID FLVB_ASPFN Reviewed; 307 AA.
AC B8NHD7;
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=NmrA-like family domain-containing oxidoreductase flvB {ECO:0000303|PubMed:31885262};
DE EC=1.-.-.- {ECO:0000269|PubMed:31885262};
DE AltName: Full=Flavunoidine biosynthesis cluster protein B {ECO:0000303|PubMed:31885262};
GN Name=flvB {ECO:0000303|PubMed:31885262}; ORFNames=AFLA_135420;
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: NmrA-like family domain-containing oxidoreductase; part of
CC the gene cluster that mediates the biosynthesis of flavunoidine, an
CC alkaloidal terpenoid with a tetracyclic cage-like core connected to
CC dimethylcadaverine via a C-N bond and acylated with 5,5-dimethyl-L-
CC pipecolate (PubMed:31885262). The tetracyclic core is synthesized by
CC the terpene cyclase flvE and the cytochrome P450 monooxygenase flvD
CC (PubMed:31885262). The terpene cyclase flvE catalyzes the cyclization
CC of farnesyl pyrophosphate (FPP) to form (1R,4R,5S)-(+)-acoradiene and
CC the cytochrome P450 monooxygenase flvD is then responsible for
CC oxidative conversion of (1R,4R,5S)-(+)-acoradiene into the tetracyclic
CC cage present in the final product flavunoidine (PubMed:31885262). The
CC cytochrome monooxygenase flvC then hydroxylates the C-10 position
CC (PubMed:31885262). The second terpene cyclase flvF is required for
CC attachment of the C-7 axial dimethylcadaverine which is itself produced
CC by the N-methyltransferase flvH and the decarboxylase flvG via
CC methylation of L-lysine to give N,N-dimethyl-L-Lysine, and
CC decarboxylation to afford dimethylcadaverine, respectively
CC (PubMed:31885262). The NRPS flvI acylates the terpenoid core at the
CC hydroxylated C-10 with dimethylpipecolate to yield final flavunoidine
CC (PubMed:31885262). The bifunctional enzyme flvA and the dehydrogenase
CC flvB are responsible for the synthesis of the dimethylpipecolate
CC precursor (PubMed:31885262). The PLP-dependent lyase domain of flvA
CC might use L-O-acetyl-homoserine and alpha-keto-isovalerate to form an
CC intermediary ketone that can cyclize intramolecularly to yield an imine
CC (PubMed:31885262). The imine can be reduced by flvB to yield the 6-
CC carboxylated pipecolate (PubMed:31885262). The C-terminal alpha-KG-
CC dependent oxygenase domain of flvA is then proposed to catalyze the
CC decarboxylation to yield dimethylpipecolate (PubMed:31885262).
CC {ECO:0000269|PubMed:31885262}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:31885262}.
CC -!- SIMILARITY: Belongs to the NmrA-type oxidoreductase family.
CC {ECO:0000305}.
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DR EMBL; EQ963478; EED50779.1; -; Genomic_DNA.
DR RefSeq; XP_002379555.1; XM_002379514.1.
DR STRING; 5059.CADAFLAP00007420; -.
DR EnsemblFungi; EED50779; EED50779; AFLA_135420.
DR VEuPathDB; FungiDB:AFLA_135420; -.
DR eggNOG; ENOG502S5T1; Eukaryota.
DR HOGENOM; CLU_007383_10_4_1; -.
DR OMA; ILYTSQM; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000001875; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR008030; NmrA-like.
DR Pfam; PF05368; NmrA; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NADP; Oxidoreductase.
FT CHAIN 1..307
FT /note="NmrA-like family domain-containing oxidoreductase
FT flvB"
FT /id="PRO_0000454478"
FT BINDING 4..9
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT BINDING 32..36
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT BINDING 53..54
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT BINDING 74..76
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HBL8"
FT BINDING 148..151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HBL8"
SQ SEQUENCE 307 AA; 34563 MW; DF67530E1D2D76A4 CRC64;
MRYLITGATG GLGGHILEYF IAQIPFSDFA ASSSSPENRS RFESRGVNFR HLDYENPTTL
NRALHDVENL LFISTNANVI DVEKVKRQHR NVVEAARKAN VKHVWYTSLP FGGLTNDSEV
SVQRAHLATE KMLKESGLTF TCIREGIYVE GFPLFLNWYP ETTLLTLPRD GEIAFTSRVE
LAVCTARLMI QGGFENRIVL LTAGETITAK ELVSVINETT GRRVELRYVS PDEFVDAGPR
NDRGGKSRAF FETLVSLWES AASGELRTMD GLMAEILGRD PIPPRDAVRQ LLVENRDHTW
HQMYAKK
