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.
Zhenbo Yuan, Huiling Liu, Fei Li et al.· Natural product reports (Pri...· 1 citation
Mogroside VI (Mog VI) is a rare triterpene glycoside from Siraitia grosvenorii with promising bioactivities. However, its biosynthesis is limited by a single rate-limiting glycosylation step converting mogroside V, catalyzed by the inherently low-activity plant glycosyltransferase UGT73-327-2. In this study, we applied a structure-guided engineering strategy to overcome this catalytic bottleneck. By combining substrate-channel expansion with catalytic pocket remodeling, the double mutant W192F/K206E was generated, showing a 22.2-fold increase in catalytic activity. Molecular dynamics simulations and kinetic analyses indicated that the enhanced performance results from an enlarged substrate-access channel, improved substrate-binding stability, and a more favorable active-site geometry that reduces key catalytic distances. Furthermore, coupling the engineered UGT with Arabidopsis thaliana sucrose synthase enabled an in situ UDP-glucose regeneration system, achieving a Mog VI titer of 5.6 g·L-1 with a 76.8% molar conversion. This work establishes an efficient biocatalytic route for Mog VI production and highlights the potential of structure-based glycosyltransferase engineering for the synthesis of rare natural glycosides.
Dong Guo, Yan Zhang, Xupeng Guo et al.· Journal of Agricultural and...· 0 citations