细胞寿命在大肠杆菌细胞工厂构建中的应用

Application of chronological lifespan in the construction of Escherichia coli cell factories

摘要:

微生物细胞工厂以可再生资源为原料，为工业化学品的可持续生产提供了一种有前景的替代方案。然而，不适的外界环境显著影响了微生物细胞的存活率，降低了微生物细胞工厂的生产性能。通过延长微生物细胞的时序寿命，可以显著提升微生物细胞工厂的生产性能。首先，基于存活率的变化建立了细胞时序寿命和半时序寿命的评价体系；然后，发现半胱氨酸、肌肽、氨基胍和氨基葡萄糖抗衰老药物可以使大肠杆菌Escherichia coli细胞的时序寿命分别延长80%、80%、50%和120%；最后，延长E. coli时序寿命可以显著改善E. coli细胞工厂的生产性能，可以用于改善具有本源代谢合成路径的E. coli细胞工厂的生产性能，使乳酸和丙酮酸的得率分别提升30.0%和25.0%，也可以用于改善具有异源代谢合成路径的E. coli细胞工厂的生产性能，使苹果酸的得率提升27.0%。这些研究结果表明延长E. coli细胞寿命提供了一种潜在的改善细胞工厂的生产性能的方法。

Abstract:

Microbial cell factories capable of producing valuable chemicals from renewable feedstocks provide a promising alternative towards sustainability. However, environmental stress remarkably affects the performance of microbial cell factories. By extending the chronological lifespan of microbial cells, the performance of microbial cell factories can be greatly improved. Firstly, an evaluation system for chronological lifespan and semi-chronological lifespan was established based on the changes in survival rates. Secondly, the addition of anti-aging drugs such as cysteine, carnosine, aminoguanidine and glucosamine increased the chronological lifespan of E. coli by 80%, 80%, 50% and 120%, respectively. Finally, we demonstrated that extending the chronological lifespan of E. coli increased the yield of metabolites produced by E. coli cell factories with endogenous (lactic acid and pyruvic acid) or exogenous (malic acid) metabolic pathway by 30.0%, 25.0%, and 27.0%, respectively. The strategy of extending chronological lifespan of E. coli provides a potential approach for enhancing the performance of microbial cell factories.