Continuous-flow chemo-enzymatic gram-scale synthesis of indole-3-acetic acid

Abstract

In this work, a chemo-enzymatic reaction was developed to synthesize indole-3-acetic acid (IAA) in a continuous flow mode. The cascade reaction consists of the oxidative decarboxylation of L-tryptophan catalyzed by tryptophan 2-monooxygenase (TMO) and the subsequent acid-catalyzed hydrolysis. The telescoped continuous-flow reaction setup was systematically designed using design equations with empirical reaction kinetics, showcasing a flow biocatalytic development framework. Optimal conditions were selected to minimize byproducts from non-specific hydrolysis. This process gave a promising space-time yield (STY) of 11.16 g L⁻¹ day⁻¹ while maintaining a high overall yield of 48.50%. This work demonstrates the feasibility of combining conventional chemical and enzymatic reactions, leveraging the strengths of both methods to enhance productivity and efficiency.