Wu Lijuan, Li Jinlong, Zhang Yahui, Tian Zhizhong, Jin Zhaoxia, Liu Linxia, Zhang Dawei
School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, China.
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
Microorganisms. 2024 May 3;12(5):933. doi: 10.3390/microorganisms12050933.
Pyridoxine, also known as vitamin B, is an essential cofactor in numerous cellular processes. Its importance in various applications has led to a growing interest in optimizing its production through microbial biosynthesis. However, an imbalance in the net production of NADH disrupts intracellular cofactor levels, thereby limiting the efficient synthesis of pyridoxine. In our study, we focused on multiple cofactor engineering strategies, including the enzyme design involved in NAD-dependent enzymes and NAD regeneration through the introduction of heterologous NADH oxidase (Nox) coupled with the reduction in NADH production during glycolysis. Finally, the engineered achieved a pyridoxine titer of 676 mg/L in a shake flask within 48 h by enhancing the driving force. Overall, the multiple cofactor engineering strategies utilized in this study serve as a reference for enhancing the efficient biosynthesis of other target products.
吡哆醇,也称为维生素B6,是众多细胞过程中必不可少的辅助因子。它在各种应用中的重要性引发了人们对通过微生物生物合成优化其生产的兴趣日益浓厚。然而,NADH净产量的失衡会破坏细胞内辅助因子水平,从而限制吡哆醇的高效合成。在我们的研究中,我们专注于多种辅助因子工程策略,包括参与NAD依赖性酶的酶设计以及通过引入异源NADH氧化酶(Nox)进行NAD再生,并减少糖酵解过程中的NADH产生。最后,通过增强驱动力,工程菌株在摇瓶中48小时内实现了676mg/L的吡哆醇滴度。总体而言,本研究中使用的多种辅助因子工程策略可为提高其他目标产物的高效生物合成提供参考。