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Xiu-Lai Chen

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Review Jul 2026

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.

Ning Jiao, Zhanpeng Shan, Xiu-Lai Chen · Biotechnology Advances · 0 citations

Aug 2026

Systematic Metabolic Engineering of Escherichia coli for High-Level Production of trans-4-Hydroxy-L-proline.

As a high-value-added amino acid derivative, trans-4-hydroxy-L-proline (T-4-Hyp) faces key bottlenecks in its microbial production from glucose, including insufficient precursor supply and an imbalance between cell growth and product biosynthesis. In this study, we successfully constructed an engineered Escherichia coli strain QF-27 for efficient T-4-Hyp production. First, the L-proline (L-Pro) biosynthetic pathway was enhanced by overexpressing the feedback-resistant γ-glutamyl kinase, glutamate-γ-semialdehyde dehydrogenase, and pyrroline-5-carboxylate reductase, and by knocking out the L-proline dehydrogenase. The resulting strain QF-9 produced 15.75 ± 0.56 g/L of L-Pro. Subsequently, the expression level of proline-4-hydroxylase from Dactylosporangium sp. RH1 was optimized in strain QF-9, and the resulting strain QF-14 produced 5.32 ± 0.26 g/L of T-4-Hyp. To address the insufficient supply of α-ketoglutarate (α-KG), a multi-modular synergistic strategy (i.e., blocking byproduct pathways, enhancing α-KG flux, and relieving global transcriptional repression) increased T-4-Hyp production to 11.02 ± 0.27 g/L. Moreover, a dynamic switch combining PrpsT promoter and DAS+4 degradation tag was designed to repress expression and promote degradation of the α-ketoglutarate dehydrogenase complex during the stationary phase, thereby balancing cell growth and T-4-Hyp production. Consequently, T-4-Hyp production reached 14.37 ± 0.46 g/L, and residual L-Pro fell to 0.38 ± 0.17 g/L. In fed-batch fermentation, the final strain QF-27 produced 105.72 ± 0.84 g/L of T-4-Hyp with productivity of 2.20 g/L/h and carbon yield of 0.364 g/g glucose. To our knowledge, this is the best performance reported for T-4-Hyp production by microbial fermentation, and the first study to enhance it via systematic modification of central carbon metabolism.

Kai Wang, Shu-Ping Tian, Shuo Wan et al. · Metabolic Engineering · 0 citations