Construction of cell factories, and multi-enzymatic and chemoenzymatic cascades to enable the efficient production of alkaloids.

Abstract

Covering: up to 2025Alkaloids constitute an invaluable reservoir for pharmaceutical discovery. However, their therapeutic development has long been constrained by the inefficiencies of plant extraction, as well as the economic impracticality of total chemical synthesis. In recent years, biomanufacturing has emerged as a transformative paradigm, enabling sustainable and scalable access to these complex molecules. This review provides an overview of the pivotal advances in alkaloid biosynthesis, delineated across de novo biosynthesis in prokaryotic and eukaryotic systems, concise multi-enzyme cascades, and chemoenzymatic synthesis. By discussing these pioneering examples, analyzing the strategic lessons, inherent limitations, and corresponding solutions for these platforms, this review illuminates how synthetic biology and biocatalysis are collectively reshaping the landscape of alkaloid production and paving the way for their expanded pharmaceutical applications.