The carbon and energy efficiency of a biomanufacturing process is of crucial importance in determining its economic viability. Formate dehydrogenase has been demonstrated to be beneficial in regenerating NADH from formate produced during sugar metabolism, thereby creating energy-efficient systems. Nevertheless, introducing enzyme(s) for butyryl butyrate (BB) biosynthesis based on this system, only 1.64 g/L BB with 14.3 % carbon yield was obtained due to an imbalance in NADH-NAD+ turnover. To address the issue of NADH accumulation, a joint redox-balanced pathway for BB biosynthesis was developed in this study by coupling acetate and glucose metabolism. Following overexpression of acetyl-CoA synthetase in the BB-producing strain, acetate and glucose were co-utilized stoichiometrically and intracellular redox homeostasis was achieved. The engineered strain produced 29.02 g/L BB with carbon yield of 43.3 %, representing the highest yield ever reported for fermentative production of BB. It indicated the potential for developing a carbon- and energy-effective route for biomanufacturing.

中文翻译：

---

构建氧化还原偶联途径共代谢葡萄糖和乙酸盐，用于在大肠杆菌中高产生产丁酸丁酯


生物制造过程的碳和能源效率对于确定其经济可行性至关重要。甲酸盐脱氢酶已被证明有利于从糖代谢过程中产生的甲酸盐中再生 NADH，从而创建节能系统。然而，基于该系统引入用于丁酰丁酸丁酯 （BB） 生物合成的酶，由于 NADH-NAD+ 周转率的不平衡，仅获得 1.64 g/L BB 和 14.3% 的碳产率。为了解决 NADH 积累的问题，本研究通过偶联乙酸盐和葡萄糖代谢开发了一种 BB 生物合成的联合氧化还原平衡途径。在产生 BB 的菌株中过表达乙酰辅酶 A 合成酶后，乙酸盐和葡萄糖在化学计量上共利用，并实现细胞内氧化还原稳态。工程菌株产生 29.02 g/L BB，碳产量为 43.3 %，代表了有史以来报告的 BB 发酵生产的最高产量。它表明了为生物制造开发碳和能源高效路线的潜力。