Acetolactate synthase (ALS)

Acetolactate synthase (ALS), also known as acetohydroxyacid synthase (AHAS), is a thiamine diphosphate-dependent enzyme that catalyzes the first step in the biosynthesis of the branched-chain amino acids valine, leucine, and isoleucine by combining two molecules of pyruvate to yield 2-acetolactate, or one pyruvate and one 2-ketobutyrate to yield 2-aceto-2-hydroxybutyrate[1][5][9]. ALS is widely conserved in plants, fungi, archaea, and bacteria, but is absent in animals, making it an excellent target for herbicidal compounds and a potential antimicrobial target[1][9]. The enzyme consists of catalytic and regulatory subunits, requires thiamine diphosphate (ThDP), magnesium ions (Mg²⁺), and sometimes FAD as cofactors[1][5][8][7]. ALS inhibitors are a major class of commercial herbicides that block amino acid synthesis, leading to plant death[9][8]. Resistance can emerge through target-site mutations, which is an ongoing agricultural challenge. In bacteria, catabolic forms (cALS) participate in fermentation pathways such as the production of acetoin and 2,3-butanediol[7][3]. No routine clinical biomarkers exist for ALS activity in medicine, but resistance mutations are agronomically important[9][8]. Safety concerns pertain mainly to herbicide selectivity and the development of resistance among weed populations.

Other names

Acetohydroxyacid synthase (AHAS)Acetolactate synthase (cALS for catabolic form)Pyruvate:pyruvate acetaldehydetransferase (decarboxylating)EC 2.2.1.6

Inhibition of ALS leads to impairment of branched-chain amino acid biosynthesis, causing growth arrest and cell death in plants and some bacteria