Acetolactate synthase

Enzyme involved in the biosynthesis of branched-chain amino acids

Acetolactate synthase

Acetolactate synthase (ALS), also known as acetohydroxyacid synthase, is an enzyme that catalyzes the first step in the biosynthesis of the branched-chain amino acids valine, leucine, and isoleucine. This enzyme is found in plants, fungi, and microorganisms, but not in animals, making it a target for herbicides and antibiotics.

Function

Acetolactate synthase catalyzes the condensation of two molecules of pyruvate to form acetolactate in the biosynthesis of valine and leucine. It also catalyzes the condensation of pyruvate and 2-ketobutyrate to form acetohydroxybutyrate in the biosynthesis of isoleucine. These reactions are the first committed steps in the biosynthetic pathways of these amino acids.

Structure

ALS is a multimeric enzyme composed of several subunits. The enzyme requires the cofactor thiamine pyrophosphate (TPP) and the metal ion magnesium for its activity. The structure of ALS has been studied extensively to understand its function and to design inhibitors that can serve as herbicides.

Inhibition

Acetolactate synthase is the target of several classes of herbicides, including the sulfonylureas, imidazolinones, and triazolopyrimidines. These herbicides inhibit ALS by binding to the enzyme and preventing it from catalyzing its reactions. The inhibition of ALS leads to the depletion of branched-chain amino acids, which is lethal to plants.

Clinical significance

While ALS is not present in animals, its inhibition is important in agriculture for controlling weed growth. The development of ALS-inhibiting herbicides has been a major advancement in crop protection. However, the widespread use of these herbicides has led to the evolution of herbicide-resistant weed species.

Biotechnological applications

ALS is used in metabolic engineering to produce branched-chain amino acids in microorganisms. By manipulating the expression of ALS and other enzymes in the pathway, it is possible to increase the yield of these amino acids for industrial purposes.

Related pages

• Branched-chain amino acid
• Herbicide resistance
• Enzyme inhibition
• Metabolic engineering

Gallery

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  Structure of acetolactate synthase