The Catalysis of Bacillus subtilis Acetolactate Synthase Is Fundamentally Underestimated

Abstract

Acetolactate synthase (ALS) is an indispensable enzyme in the catabolic pathway for the biotransformation of diacetyl and 2,3-butandiol. It has been established that the protein only ligates two molecules of pyruvate to afford (S)-acetolactate. Our investigations, however, have revealed that besides its fundamental reaction, ALS of Bacillus subtilis (BsALS) catalyzes the condensation of pyruvate and 2-ketobutyrate to produce not only (S)-acetolactate and (S)-acetohydroxybutyrate using pyruvate as a donor substrate and pyruvate/2-ketobutyrate as acceptor substrates, but also (S)-propionyllactate and (S)-propionylhydroxybutyrate by utilizing 2-ketobutyrate as a donor substrate and pyruvate/2-ketobutyrate as acceptor substrates. Moreover, the enzyme mediates ligation reactions by utilizing pyruvate or 2-ketobutyrate as a donor substrate and benzylaldehyde or nitrosobenzene as an acceptor substrate to generate chiral arylacylcarbinols or arylhydroxamic acids, respectively. All experimental evidence suggests that the catalytic potential of BsALS has been significantly underestimated, and this enzyme holds immense promise for asymmetric synthesis of diverse chiral α-hydroxyketones as well as in the preparation of arylhydroxamic acids.