Chen Kai, Liu Linxia, Li Jinlong, Tian Zhizhong, Jin Hongxing, Zhang Dawei
School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, China.
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
Synth Syst Biotechnol. 2024 Mar 20;9(2):388-398. doi: 10.1016/j.synbio.2024.03.005. eCollection 2024 Jun.
Vitamin B plays a crucial role in cellular metabolism and stress response, making it an essential component for growth in all known organisms. However, achieving efficient biosynthesis of vitamin B faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production. In this study, our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase (SerC) to resolve its redundancy and promiscuity. The enzyme SerC was semi-designed and screened based on sequences and predicted values, respectively. Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B. The resulting strain enhances the production of vitamin B, indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B. This study presents a promising strategy to address the challenge posed by multifunctional enzymes, with significant implications for enhancing biochemical production through engineering processes.
维生素B在细胞代谢和应激反应中起着至关重要的作用,使其成为所有已知生物体生长的必需成分。然而,实现维生素B的高效生物合成面临着在生长和生产之间维持代谢通量平衡分布的挑战。在本研究中,我们的重点是通过对磷酸丝氨酸转氨酶(SerC)进行工程改造来解决其冗余性和混杂性,从而应对这一挑战。分别基于序列和预测值对SerC酶进行了半设计和筛选。然后对显示出潜力的突变体和异源蛋白进行微调,以优化维生素B的生产。所得菌株提高了维生素B的产量,表明不同的通量被分配到丝氨酸和维生素B的生物合成途径。本研究提出了一种有前景的策略来应对多功能酶带来的挑战,对通过工程过程提高生化产物产量具有重要意义。