Recent advances in decoding biosynthetic pathways and synthetic biology approaches for plant alkaloids.

Abstract

Covering: 2018 to 2025Alkaloids represent a large and structurally diverse class of natural products predominantly found in plants and rarely in animals. Well-known compounds such as vinblastine, berberine, and scopolamine exhibit remarkable pharmaceutical potential, with several already in clinical use. These plant-derived alkaloids have attracted enduring interest due to their diversity, structural complexity, and pronounced biological activities, making them a privileged resource for drug discovery. In recent years, breakthrough advances have been made in elucidating the biosynthetic pathways of plant alkaloids, making this a highly promising research field. Successful cases including reserpine, strychnine, and hyoscyamine have not only provided novel strategies for drug development and sustainable production, but also greatly stimulated scientific enthusiasm. In this review, we focus on representative plant alkaloids from major classes including monoterpene indole alkaloids (MIAs), tetrahydroisoquinoline alkaloids (THIQAs), tropane alkaloids (TAs), and other types, covering the period from 2018 to 2025. It highlights key challenges in pathway elucidation, including stereochemical control (R/S configuration), important cyclization, and tailoring modifications particularly those catalyzed by specific enzymes. This review also covers catalytic sequence determination, and innovative approaches for long-pathway decoding. Furthermore, we discuss how synthetic biology and metabolic engineering strategies enable efficient and sustainable microbial production of these compounds. By identifying common obstacles and proposing effective solutions, this review aims to inspire researchers engaged in functional gene characterization, synthetic biosystems development, yield optimization, and drug innovation for plant alkaloids. It seeks to promote interdisciplinary collaboration across botany, chemistry, biology, and pharmaceutical sciences, thereby accelerating the discovery and scalable production of high-value plant alkaloids.