Ketol-acid reductoisomerase (KARI)

Ketol-acid reductoisomerase (KARI) is a magnesium-dependent, NADPH-utilizing bifunctional enzyme that catalyzes two sequential reactions in the biosynthesis of branched-chain amino acids (valine, leucine, and isoleucine) in bacteria, plants, and fungi but not in animals[1][2][3][4][5]. It orchestrates an alkyl migration (isomerization) followed by a reductive step using NADPH[2][3]. There are two main KARI classes: the short form, found in fungi and many bacteria, and the long form, found in plants and some bacteria[1][2]. The enzyme is essential for growth and survival in organisms that rely on de novo synthesis of branched-chain amino acids[4]. KARI is the target of several herbicides and is under investigation as a potential antibacterial and antifungal target given its absence in animal metabolism[4][7][8]. Structurally, KARI forms oligomeric assemblies (dimers, tetramers, or dodecamers) and relies on conserved residues to coordinate metal ions and catalyze the reaction[1][3]. Inactivation of KARI disrupts branched-chain amino acid synthesis, leading to growth arrest in sensitive organisms[4]. KARI’s unique role in non-animal organisms makes it an attractive target in agriculture and anti-infective research.

Other names

Ketol-acid reductoisomerase (NADP(+))Keto-acid reductoisomeraseILVC (especially in fungal literature)EC 1.1.1.86

Competitive inhibition of substrate binding or cofactor (NADPH or Mg2+) binding; Disruption of branched-chain amino acid biosynthesis, leading to amino acid starvation