Vitamin B6 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 B6 faces the challenge ...Vitamin B6 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 B6 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 kcat values,respectively.Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6.The resulting strain enhances the production of vitamin B6,indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6.This study presents a promising strategy to address the challenge posed by multifunctional enzymes,with significant implications for enhancing biochemical production through engineering processes.展开更多
基金This work was supported by the National Key R&D Program of China(2022YFC2106100)National Natural Science Foundation of China(22178372,32200049)+2 种基金National Science Fund for Distinguished Young Scholars(22325807)Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-011,TSBICIP-CXRC-055)Yellow River Delta Industry Leading Talents(DYRC20190212).
文摘Vitamin B6 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 B6 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 kcat values,respectively.Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6.The resulting strain enhances the production of vitamin B6,indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6.This study presents a promising strategy to address the challenge posed by multifunctional enzymes,with significant implications for enhancing biochemical production through engineering processes.
