ID   BEA2_GIBIN              Reviewed;         390 AA.
AC   G3GBU6;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   16-NOV-2011, sequence version 1.
DT   03-AUG-2022, entry version 27.
DE   RecName: Full=Ketoisovalerate reductase BEA2 {ECO:0000303|PubMed:22916830};
DE            Short=KIVR {ECO:0000303|PubMed:22916830};
DE            EC=1.2.7.- {ECO:0000269|PubMed:22916830};
OS   Gibberella intermedia (Bulb rot disease fungus) (Fusarium proliferatum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC   Fusarium fujikuroi species complex.
OX   NCBI_TaxID=948311;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC   STRAIN=LF061;
RX   PubMed=23832252; DOI=10.1007/s11427-013-4505-1;
RA   Zhang T., Zhuo Y., Jia X., Liu J., Gao H., Song F., Liu M., Zhang L.;
RT   "Cloning and characterization of the gene cluster required for beauvericin
RT   biosynthesis in Fusarium proliferatum.";
RL   Sci. China Life Sci. 56:628-637(2013).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP   REGULATION.
RC   STRAIN=LF061;
RX   PubMed=22916830; DOI=10.1186/1472-6750-12-55;
RA   Zhang T., Jia X., Zhuo Y., Liu M., Gao H., Liu J., Zhang L.;
RT   "Cloning and characterization of a novel 2-ketoisovalerate reductase from
RT   the beauvericin producer Fusarium proliferatum LF061.";
RL   BMC Biotechnol. 12:55-55(2012).
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:23832252, PubMed:22916830). Ketoisovalerate reductase BEA2
CC       catalyzes the NADPH-specific reduction of ketoisovaleric acid to
CC       hydroxyisovalerate, a precursor for beauvericin biosynthesis
CC       (PubMed:23832252, PubMed:22916830). The nonribosomal cyclodepsipeptide
CC       synthetase BEA1 then catalyzes the formation of beauvericin via
CC       condensation and cyclization of 3 dipeptidol monomers, each composed of
CC       one unit of hydroxyisovalerate and one unit of N-methyl-phenylalanine
CC       (By similarity). {ECO:0000250|UniProtKB:B6D9A8,
CC       ECO:0000269|PubMed:22916830, ECO:0000269|PubMed:23832252}.
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:0000269|PubMed:22916830};
CC   -!- ACTIVITY REGULATION: The reductase activity is increased by Mg(2+)
CC       (195%), Ca(2+) (169%) and slightly increased by K(+) (123%)
CC       (PubMed:22916830). The reduction activity is inhibited by Fe(2+) and
CC       Co(2+), and almost totally inhibited by Cu(2+), Mn(2+), Zn(2+) and
CC       Fe(3+) (from 3% to 9% residual activity respectively)
CC       (PubMed:22916830). The chelating agent EDTA had little effect,
CC       suggesting Mg(2+) and Ca(2+) are not determining factors, though they
CC       could promote the reductase enzyme activity (PubMed:22916830).
CC       {ECO:0000269|PubMed:22916830}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7.5. {ECO:0000269|PubMed:22916830};
CC       Temperature dependence:
CC         Optimum temperature is 35 degrees Celsius.
CC         {ECO:0000269|PubMed:22916830};
CC   -!- SIMILARITY: Belongs to the ketopantoate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; JF826561; AEN14637.1; -; Genomic_DNA.
DR   AlphaFoldDB; G3GBU6; -.
DR   SMR; G3GBU6; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.1040.10; -; 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   Pfam; PF02558; ApbA; 1.
DR   Pfam; PF08546; ApbA_C; 1.
DR   SUPFAM; SSF48179; SSF48179; 1.
PE   1: Evidence at protein level;
KW   NADP; Oxidoreductase.
FT   CHAIN           1..390
FT                   /note="Ketoisovalerate reductase BEA2"
FT                   /id="PRO_0000442153"
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"
SQ   SEQUENCE   390 AA;  43061 MW;  0DCCCB764DBD07A6 CRC64;
     MTSQEHPNWL TALLVDTRPP PKLFAWSPAN IQPKLDEGID MGSSNSDEEY DNDACVCQST
     DSDQRIYIIG PGNIGRLYAT HMARHPNALP ITLVVHRKEL LSQWVACEGV GLADITSGKL
     FLNKGFTVEW WTETRPPYGP VKEVADGKKL HNVFISTKAE AGLAEADRIR RYLGRCSSVV
     FAQNGVCKLW PPHGPLYISH RYPSGDTPTF SACVVSHGVA SAGPFLSVHA APADAYIGPV
     FWASDPESPW RHPSDDFFIR HIATTPHVNT KQVSSGEIWL LQLEKLVMNA AINPLTALLR
     CKTGELFTSY GSDDPLALVI DKLLWQTSAV IQGLVDHKTS HSVITSYAEH MSQPGTSCSV
     PKVRKKLMER FSQPILKAKL GWEEDRDTGL