Metabolic Engineering of Corynebacterium glutamicum for Producing Different Types of Triterpenoids

作者：Jingzhi Li, Xin Wang, Xahnaz Xokat, Ya Wan, Xiaopeng Gao, Ying Wang, Chun Li · 发表于：ACS Synthetic Biology · 年份：2025 · DOI：10.1021/acssynbio.4c00737 · 被引用次数：7 · 研究领域：Microbial Metabolic Engineering and Bioproduction、Plant biochemistry and biosynthesis、Pharmacological Effects of Natural Compounds

Triterpenoids widely exist in nature with diverse structures and possess various functional properties and biological effects. However, research on triterpenoids biosynthesis in Corynebacterium glutamicum is still limited to squalene, which restricts the development of C. glutamicum to produce high-value triterpenoids. In this study, C. glutamicum was developed as an efficient and flexible platform for the biosynthesis of different types of triterpenoids. Squalene was synthesized and the titer was improved to 400.1 mg/L in flask combining strategies of metabolic engineering and fermentation optimization. Particularly, intracellular squalene accounted for more than 97%, addressing the problem of leaking squalene in C. glutamicum, which may restrict the subsequent synthesis of other triterpenoids derived from squalene. Furthermore, 201.9 mg/L (3S)-2,3-oxidosqualene (SQO) and 264.9 mg/L (3S,22S)-2,3,22,23-dioxidosqualene (SDO) were successfully synthesized in strains harboring heterogeneous squalene epoxidase from Arabidopsis thaliana with different expression strengths. Therefore, a platform for de novo triterpenoids synthesis based on SQO or SDO was constructed in C. glutamicum . For instance, biosynthesis of α-amyrin and α-onocerin was achieved for the first time by introducing oxidosqualene cyclases in SQO- and SDO-producing C. glutamicum strains, respectively. After optimization, the titer of α-amyrin and α-onocerin was improved to 65.3 and 136.85 mg/L, respectively. Furthe...