Engineered microorganisms unlock a new era of diterpenoid biomanufacturing: recent advances and future perspectives

Synthetic biomanufacturing of triterpenoids: From laboratory to industry.

Triterpenoids are important natural secondary metabolites with diverse bioactivities, including antioxidant, anti-inflammatory, and anti-cancer properties, making them valuable for applications in the pharmaceutical, cosmetic, and food industries. Currently, triterpenoids are mainly obtained through natural extraction or chemical synthesis. However, these conventional approaches are often limited by production efficiency, environmental burdens, and product diversity. Rapid advances in metabolic engineering and synthetic biology have promoted the emergence of heterologous biosynthesis as a promising, efficient, and sustainable strategy for triterpenoids production. In this review, we first summarize the classification and bioactive properties of triterpenoids, together with the challenges and potential solutions associated with their microbial synthesis. Then, we analyze the key characteristics of microbial hosts and their corresponding biosynthetic pathways for triterpenoids production, aiming to establish programmable platforms that overcome the limitations of natural biosynthesis. Subsequently, we propose metabolic engineering and synthetic biology strategies, including enzyme optimization, pathway optimization, compartmentalization engineering, and systems biology approaches, for optimizing matter and energy transmission and thereby enhancing triterpenoids production. We further discuss the potential challenges for scaling up triterpenoids production from laboratory-scale studies to industrial-scale applications, including the optimization of large-scale fermentation process and the improvement of downstream extraction and recovery. Finally, we discuss the techno-economic feasibility and industrial prospects of microbial triterpenoid production, highlight current regulation and governance in synthetic biology related to triterpenoids biosynthesis, analyze existing limitations, and propose potential solutions to provide insights for future research on the biomanufacturing of triterpenoids.

Recent Advances in Bioproduction of Diols: From Concept to Commercialization.

Harnessing yeast for polyhydroxyalkanoates (PHAs) production: Challenges, engineering strategies, and future prospects.

This review provides the current state of PHAs production from wild yeast strains and the various approaches that have been used to improve yield, and discusses the performance, challenges, and limitations of various synthetic biology and metabolic engineering strategies in yeast strains for PHAs production.

Programmable plant chassis for sustainable biomanufacturing of high-value natural products.

Biomanufacturing has emerged as a strategic emerging industry worldwide, offering sustainable alternatives to conventional chemical manufacturing. To support this development, diverse production chassis have been developed, including microorganisms, mammalian cell culture systems, and plant-based platforms. Among these, plants represent a promising chassis for the biosynthesis of high-value products, as they directly fix CO₂ through photosynthesis and possess sophisticated metabolic networks that facilitate the production of structurally complex molecules. Recent advances in synthetic biology have increased the programmability of plant systems and enabled their development as engineered production chassis for the production of high-value products. This review integrates recent advances in natural and synthetic genetic elements including promoters, terminators, and transcription factors (TFs) that facilitate chassis development are summarized. Recent advances in the elucidation, reconstruction, and optimization of biosynthetic pathways for representative classes of valuable compounds, including alkaloids, terpenoids, and phenylpropanoids, are then highlighted, with particular emphasis on pathway engineering strategies that enhance productivity. Finally, we outline the key challenges and future perspectives for the large-scale industrial applications of plant chassis. This review provides a comprehensive and timely perspective on plant-based biomanufacturing, offering conceptual guidance and practical insights for advancing plant chassis from laboratory research to sustainable industrial applications.

Sclareol Production Driven by Advanced Synthetic Biology Strategies

Sclareol, a plant-derived diterpene, holds significant industrial value in perfumery, pharmaceuticals, and agriculture. Traditional production from Salvia sclarea or chemical synthesis has faced challenges such as low yield, high cost, and sustainability concerns. Recent advances in synthetic biology and metabolic engineering have enabled sclareol biosynthesis in microbial chassis cells. This Review systematically examines synthetic biology-driven strategies for improving sclareol production, with particular emphasis on microbial chassis engineering, metabolic pathway optimization, and enzyme engineering. Emerging approaches such as AI-assisted prediction, multiomics analysis, high-throughput screening, and intelligent fermentation technologies are also highlighted. Achievements and challenges in microbial sclareol biosynthesis are critically analyzed, and strategic priorities for future development are proposed. This paper provides a comprehensive reference for science and practice, aiming to advance the sustainable biomanufacturing of high-value plant-derived terpenoids.

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

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.