Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China.
Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China; Qingdao Special Food Research Institute, Qingdao 266109, China.
Bioresour Technol. 2021 Mar;324:124624. doi: 10.1016/j.biortech.2020.124624. Epub 2020 Dec 28.
With the development and application of synthetic biology, significant progress has been made in the production of folate by microbial fermentation using cell factories, especially for using generally regarded as safe (GRAS) microorganism as production host. In this review, the physiological functions and applications of folates were firstly discussed. Second, the current advances of folate-producing GRAS strains development were summarized. Third, the applications of synthetic biology-based metabolic regulatory tools in GRAS strains were introduced, and the progress in the application of these tools for folate production were summarized. Finally, the challenges to folates efficient production and corresponding emerging strategies to overcome them by synthetic biology were discussed, including the construction of biosensors using tetrahydrofolate riboswitches to regulate metabolic pathways, adaptive evolution to overcome the flux limitations of the folate pathway. The combination of new strategies and tools of synthetic biology is expected to further improve the efficiency of microbial folate synthesis.
随着合成生物学的发展和应用，利用细胞工厂通过微生物发酵生产叶酸取得了重大进展，特别是使用通常被认为是安全的（GRAS）微生物作为生产宿主。在本文中，首先讨论了叶酸的生理功能和应用。其次，总结了叶酸产生的 GRAS 菌株开发的最新进展。第三，介绍了基于合成生物学的代谢调控工具在 GRAS 菌株中的应用，并总结了这些工具在叶酸生产中的应用进展。最后，讨论了通过合成生物学提高叶酸生产效率所面临的挑战和新兴策略，包括使用四氢叶酸核糖开关构建生物传感器来调节代谢途径，适应性进化以克服叶酸途径的通量限制。预计新的策略和工具的结合将进一步提高微生物叶酸合成的效率。
