Constructing a multienzyme cascade redox-neutral system for the synthesis of halogenated indoles

Inspired by biocatalytic retrosynthesis, a multienzyme cascade system containing alcohol dehydrogenase, flavin-dependent halogenase and flavin reductase was developed for the synthesis of several halogenated indoles starting from amino alcohol. This redox-neutral system not only omitted co-substrate for nicotinamide cofactor (NADH) regeneration but also showed relatively higher conversion and chemoselectivity compared with individual biotransformation. Artificial nicotinamide cofactor (BNAH) was employed to replace NADH and flavin reductase for simplifying this system, providing a more convenient strategy for halogenated indoles.