ID BEA2_GIBF5 Reviewed; 452 AA.
AC S0EGG0;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 22-FEB-2023, entry version 33.
DE RecName: Full=Ketoisovalerate reductase BEA2 {ECO:0000303|PubMed:27750383};
DE Short=KIVR {ECO:0000303|PubMed:27750383};
DE EC=1.2.7.- {ECO:0000250|UniProtKB:G3GBU6};
DE AltName: Full=Beauvericin biosynthesis cluster protein 2 {ECO:0000303|PubMed:27750383};
GN Name=BEA2 {ECO:0000303|PubMed:27750383}; ORFNames=FFUJ_09295;
OS Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS and foot rot disease fungus) (Fusarium fujikuroi).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=1279085;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA Tudzynski B.;
RT "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT novel metabolites.";
RL PLoS Pathog. 9:E1003475-E1003475(2013).
RN [2]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27750383; DOI=10.1111/1462-2920.13576;
RA Niehaus E.M., Studt L., von Bargen K.W., Kummer W., Humpf H.U., Reuter G.,
RA Tudzynski B.;
RT "Sound of silence: the beauvericin cluster in Fusarium fujikuroi is
RT controlled by cluster-specific and global regulators mediated by H3K27
RT modification.";
RL Environ. Microbiol. 18:4282-4302(2016).
CC -!- FUNCTION: Ketoisovalerate reductase; part of the gene cluster that
CC mediates the biosynthesis of beauvericin (BEA), a non-ribosomal cyclic
CC hexadepsipeptide that shows antibiotic, antifungal, insecticidal, and
CC cancer cell antiproliferative and antihaptotactic activity
CC (PubMed:27750383). Ketoisovalerate reductase BEA2 catalyzes the NADPH-
CC specific reduction of ketoisovaleric acid to hydroxyisovalerate, a
CC precursor for beauvericin biosynthesis (By similarity). The
CC nonribosomal cyclodepsipeptide synthetase BEA1 then catalyzes the
CC formation of beauvericin via condensation and cyclization of 3
CC dipeptidol monomers, each composed of one unit of hydroxyisovalerate
CC and one unit of N-methyl-phenylalanine (By similarity).
CC {ECO:0000250|UniProtKB:B6D9A8, ECO:0000250|UniProtKB:G3GBU6,
CC ECO:0000269|PubMed:27750383}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-2-hydroxy-3-methylbutyrate + NADP(+) = 3-methyl-2-
CC oxobutanoate + H(+) + NADPH; Xref=Rhea:RHEA:62268, ChEBI:CHEBI:11851,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:145660; Evidence={ECO:0000250|UniProtKB:G3GBU6};
CC -!- INDUCTION: Expression is highly repressed by the histone deacetylase
CC HDA1 and the beauvericin cluster-specific repressor BEA4
CC (PubMed:27750383). BEA biosynthesis is also repressed by the activity
CC of the H3K27 methyltransferase KMT6 (PubMed:27750383).
CC {ECO:0000269|PubMed:27750383}.
CC -!- DISRUPTION PHENOTYPE: Decreases the production of beauvericin
CC (PubMed:27750383). {ECO:0000269|PubMed:27750383}.
CC -!- SIMILARITY: Belongs to the ketopantoate reductase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; HF679031; CCT73879.1; -; Genomic_DNA.
DR AlphaFoldDB; S0EGG0; -.
DR SMR; S0EGG0; -.
DR STRING; 1279085.S0EGG0; -.
DR EnsemblFungi; CCT73879; CCT73879; FFUJ_09295.
DR VEuPathDB; FungiDB:FFUJ_09295; -.
DR HOGENOM; CLU_031468_9_0_1; -.
DR OrthoDB; 1354873at2759; -.
DR Proteomes; UP000016800; Chromosome 9.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR013752; KPA_reductase.
DR InterPro; IPR013332; KPR_N.
DR PANTHER; PTHR43765; 2-DEHYDROPANTOATE 2-REDUCTASE-RELATED; 1.
DR PANTHER; PTHR43765:SF2; 2-DEHYDROPANTOATE 2-REDUCTASE-RELATED; 1.
DR Pfam; PF02558; ApbA; 1.
DR Pfam; PF08546; ApbA_C; 1.
DR SUPFAM; SSF48179; 6-phosphogluconate dehydrogenase C-terminal domain-like; 1.
PE 2: Evidence at transcript level;
KW NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..452
FT /note="Ketoisovalerate reductase BEA2"
FT /id="PRO_0000442151"
FT ACT_SITE 285
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 70..75
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 289
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 293
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 393
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
FT BINDING 405
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P0A9J4"
SQ SEQUENCE 452 AA; 50063 MW; 352C85E82C8501EB CRC64;
MASQEHPNWL TALLADTRPP PKLFAWSPAN IQPKLDEGID MGSSNSDEEY DNDACVCPST
DSDQRIYIIG PGNIGRLYAT HMARHPNALP ITLVVHRKEL LSQWAACEGV GLADLTSGKI
FLNKRFTVEW WTETRPPYGP VKEVADGKKL HNVFISTKAE AGLSEADRIR RYLGRCSSVV
FAQNGVCKLW PPHGPLYISH RYPSGDTPTF SACVVSHGVA SAGPFLSVHA APADAYIGPV
FWASDPESPW RQPSDDFFIR HIATTPLVNT KQVSSGEIWL LQLEKLVMNA AINPLTALLR
YKTGELFTSY GSDDPLARVI DKLLWQTSAV IQGLIDHETS HSVITSYAEQ MSQPGTSCSV
PKVRKKLTER FSQPILKAKL YAFGLKIFEH RSSMLQDIEA GRKTEIRDFN GWIVDTACFL
GTGLDVSVHS GLTGLIERCE RFDKMELGRA LL
//
