Targeting metabolic driving and minimization of by‐products synthesis for high‐yield production of D‐pantothenate in <i>Escherichia coli</i>
Bo Li, Bo Zhang, Pei Wang, Xue Cai, Yaqun Tang, Jie‐Yi Jin, Jin‐Xi Liang, Zhi‐Qiang Liu, Yu‐Guo Zheng
Abstract
Abstract Background d ‐Pantothenate (DPA) is an important functional chemical that has been widely applied in healthcare, cosmetics, animal food, and feed industries. Methods and Results In this study, a high‐yield DPA‐producing strain was constructed by metabolic engineering strategies with targeting metabolic driving and by‐products minimization. The metabolic driving force of push and pull was firstly obtained to improve the production of DPA via enrichment of precursor pool and synthetic pathway, accumulating 4.29 g L −1 DPA in shake flask fermentation. To eliminate the metabolic pressure on DPA production, an amino throttling system was proposed and successfully attenuated the synthesis of four competitive amino acids by a single‐step regulation of gdhA . Further minimization of acetate was carried out by pta deletion, and utilization of β‐alanine was improved via enhancing its uptake system with producing 5.78 g L −1 DPA. Finally, the engineered strain produced 66.39 g L −1 DPA with β‐alanine addition in fermentor under fed‐batch fermentation. Conclusion This study paved a foundation for the industrial production of DPA.