Oleanane-type pentacyclic triterpenoids are a class of naturally occurring specialized metabolites with diverse biological activities. Conventional plant extraction and chemical synthesis are constrained by low yields, high costs, and a reliance on natural resources. With the development of synthetic biology and metabolic engineering, the biosynthetic pathways of these compounds can now be systematically reconstructed and optimized, providing new opportunities for efficient production. This review summarizes the classification of oleanane-type pentacyclic triterpenoids and outlines their biosynthetic pathways and recent progress in production platforms such as plant in vitro culture and microbial cell factories. In addition, we discuss major engineering strategies used to improve triterpenoid production, including increasing precursor supply, reducing competing pathways, implementing enzyme engineering and engineering cofactors, improving protein performance, subcellular compartmentalization, enhancing transport, and optimizing fermentation conditions. In view of the current progress, this review also identifies persistent challenges in the biosynthesis of these compounds and outlines potential strategies to address them.
Fu-Yan Yuan, De-Yue Diao, Shi-Xiang Peng et al.· Journal of Agricultural and...· 0 citations
l-arginine is widely used in food, feed, pharmaceutical, and cosmetic industries. However, its industrial-scale biosynthesis is limited by insufficient coordination between metabolic regulation, pathway engineering, and fermentation optimization. In this study, an enzyme-constrained model (ec_iML1515) was used to identify 11 gene targets affecting l-arginine production. Based on these targets, metabolic reprogramming was performed in strain Arg4 to rebalance precursor pools (oxaloacetate, aspartate, and citrulline), generating strain Arg10 with an l-arginine titer of 87.24 g/L. Subsequently, the rate-limiting enzyme argininosuccinate synthetase (ArgG) was engineered to the optimal mutant ArgGY131F/K132R and genomically integrated to construct the strain Arg11, increasing the l-arginine titer to 94.80 g/L while reducing aspartate accumulation 7.6-fold to 1.1 g/L. Finally, after the optimization of fermentation temperature and pH, the l-arginine titer, yield, and productivity of strain Arg11 were 114.18 g/L, 0.57 g/g, and 2.27 g/L/h, respectively, in a 3-m3 fermenter, achieving the best performance reported to date.
Shengyang He, Qi Sheng, Gang Men et al.· Bioresource Technology· 0 citations
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