A Modular Chemoenzymatic Cascade Simplifies Divergent Synthesis of Natural and Unnatural Benzylisoquinoline Alkaloids.

ABSTRACT: Conventional chemical or biological synthetic methods often encounter challenges in conveniently preparing chiral natural and unnatural products with the same skeleton at a scalable level, due to their complexity with numerous chiral centers or uncharacterized enzymes. Herein, a simplified modular chemoenzymatic platform is designed featuring a streamlined four-enzyme cascade coupled with a chemical module that involves one or two chemical steps. This platform enables the divergent synthesis of structurally diverse natural and unnatural benzylisoquinoline alkaloids (BIAs), including 1-benzylisoquinoline, protoberberine, morphinan, and aporphine alkaloids. Moreover, the enantioselectivity of the chiral BIAs is up to 99% ee. The titer of papaverine reaches an impressive 2.83 g L^-1

SUBMITTER: Liu H 

PROVIDER: S-EPMC12766994 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature