Acetohydroxyacid synthase (AHAS)

Acetohydroxyacid synthase (AHAS; also known as acetolactate synthase, ALS) is a thiamine diphosphate-dependent enzyme, classified as EC 2.2.1.6, and catalyzes the first common step in the biosynthesis of the branched-chain amino acids valine, leucine, and isoleucine. AHAS catalyzes the condensation of two pyruvate molecules (or pyruvate and 2-ketobutyrate) to give acetolactate (or acetohydroxybutyrate), precursors for these essential amino acids. This metabolic pathway is present in plants, fungi, archaea, and bacteria, but not in animals, making AHAS a major target for herbicides and a potential antibiotic target. The effectiveness of multiple classes of commercial herbicides is due to their selective inhibition of plant AHAS, enabling high crop-versus-weed selectivity and low animal toxicity. The enzyme consists of catalytic and regulatory subunits, requires thiamine pyrophosphate (TPP/ThDP) as a cofactor, and is highly conserved, with resistance mutations compromising herbicide efficacy increasingly reported in agricultural settings.

Other names

Acetolactate synthase (ALS)Acetohydroxy acid synthasePyruvate:pyruvate acetaldehydetransferase (decarboxylating)EC 2.2.1.6

Competitive or noncompetitive inhibition of substrate binding at the ThDP (thiamine diphosphate) cofactor site; Occupation of active-site channel, blocking access of pyruvate and 2-ketobutyrate, leading to amino acid starvation in organisms reliant on the pathway; Certain herbicides also lead to cofactor degradation or inactivation (e.g., ThDP cleavage or modification)