State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Disruptive & Sustainable Technologies for Agricultural Precision, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore.
Bioresour Technol. 2024 Jun;402:130774. doi: 10.1016/j.biortech.2024.130774. Epub 2024 May 1.
Formate as an ideal mediator between the physicochemical and biological realms can be obtained from electrochemical reduction of CO and used to produce bio-chemicals. Yet, limitations arise when employing natural formate-utilizing microorganisms due to restricted product range and low biomass yield. This study presents a breakthrough: engineered Corynebacterium glutamicum strains (L2-L4) through modular engineering. L2 incorporates the formate-tetrahydrofolate cycle and reverse glycine cleavage pathway, L3 enhances NAD(P)H regeneration, and L4 reinforces metabolic flux. Metabolic modeling elucidates C1 assimilation, guiding strain optimization for co-fermentation of formate and glucose. Strain L4 achieves an OD of 0.5 and produces 0.6 g/L succinic acid. C-labeled formate confirms C1 assimilation, and further laboratory evolution yields 1.3 g/L succinic acid. This study showcases a successful model for biologically assimilating formate in C. glutamicum that could be applied in C1-based biotechnological production, ultimately forming a formate-based bioeconomy.
通过电化学还原 CO 可以获得作为理化和生物领域理想媒介的甲酸盐，并将其用于生产生化制品。然而，由于产物范围受限和生物质产量低，使用天然甲酸盐利用微生物时会出现限制。本研究通过模块化工程提供了一个突破：工程化谷氨酸棒杆菌菌株（L2-L4）。L2 中整合了甲酸盐-四氢叶酸循环和反向甘氨酸裂解途径，L3 增强了 NAD(P)H 再生，L4 加强了代谢通量。代谢建模阐明了 C1 同化作用，指导菌株优化用于甲酸盐和葡萄糖的共发酵。菌株 L4 的 OD 值达到 0.5，产生 0.6 g/L 琥珀酸。C 标记的甲酸盐证实了 C1 的同化作用，进一步的实验室进化产生了 1.3 g/L 琥珀酸。本研究展示了在谷氨酸棒杆菌中生物同化甲酸盐的成功模型，该模型可应用于基于 C1 的生物技术生产，最终形成基于甲酸盐的生物经济。
