A concise enzyme cascade enables the manufacture of natural and halogenated protoberberine alkaloids.

ABSTRACT: The application and drug development of plant-derived natural products are often limited by their low abundance in medicinal plants and the lack of structural complexity and diversity. Herein, we design a concise enzyme cascade to efficiently produce natural and unnatural protoberberine alkaloids from cost-effective, readily available substrates. Through enzyme discovery and engineering, along with systematic optimization of the berberine bridge enzyme to address remaining manufacturing challenges in protoberberine alkaloid biosynthesis, the high production of drug Rotundine is achieved at an impressive gram-scale titer, demonstrating its industrial potential. More importantly, this cascade also enables the efficient biosynthesis of various unnatural halogenated protoberberine alkaloids. T

SUBMITTER: Li F 

PROVIDER: S-EPMC11847921 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature