Enzymatic synthesis of health-beneficial oligoindoles using peroxidase†

Abstract

Diets can maintain good health and influence responses to therapeutic agents, as exemplified by cruciferous vegetables, a privileged source of health-beneficial oligoindoles such as DIM (marketed as “nutraceutical”), LTr1, LTe2, and LTr3. All of these oligoindoles have been identified as anti-cancer agents. However, access to these oligoindoles currently remains largely unreliable since their chemical synthesis and isolation from vegetables are challenging, cost-ineffective, and eco-unfriendly, thereby limiting their development. Herein, we present a horseradish peroxidase (HRP)-catalysed method for the synthesis of DIM, LTr1, LTe2, and LTr3 from indole-3-acetic acid (IAA) mixed with indole or its commercially available derivatives. Moreover, green chemistry metrics and EcoScale score evaluations supported the enzymatic method as a green protocol. By gaining insights into enzymatic mechanisms, which involve the radical–radical coupling reaction, the whole-cell biosynthesis of bioactive oligoindoles can be achieved. Altogether, the work provides an efficient access to cruciferous vegetable-derived oligoindoles, deepens our understanding of the application potential of HRP, and promotes further development of synthetic biology methods for DIM, LTr1, and LTe2.