基于图论和约束优化的异源代谢途径设计方法及应用

构建高产高附加值产品的微生物细胞工厂是代谢工程的研究目标之一,设计高效的产品合成途径是实现这一目标的重要方式.不同微生物底盘因其代谢能力有所差异,故而可以利用的底物和生产的产品范围有限.为了扩大其生产能力,需要进行代谢途径从无到有的设计.传统代谢工程基于经验进行异源途径设计的方式低效且无法确保结果的全面性,而系统生物学...

Graph-based and constraint-based heterologous metabolic pathway design methods and application

It is among the goals in metabolic engineering to construct microbial cell factories producing high-yield and high value-added target products,and an important solution is to design efficient synthetic pathway for the target products.However,due to the difference in metabolic capacity among microbial chassises,the available substrate and the yielded products are limited.Therefore,it is urgent to design related metabolic pathways to improve the production capacity.Existing metabolic engineering approaches to designing heterologous pathways are mainly based on biological experience,which are inefficient.Moreover,the yielded results are in no way comprehensive.However,systems biology provides new methods for heterologous pathway design,particularly the graph-based and constraint-based methods.Based on the databases containing rich metabolism information,they search for and uncover possible metabolic pathways with designated strategy (graph-based method) or algorithm (constraint-based method) and then screen out the optimal pathway to guide the modification of strains.In this paper,we reviewed the databases and algorithms for pathway design,and the applications in metabolic engineering and discussed the strengths and weaknesses of existing algorithms in practical application,hoping to provide a reference for the selection of optimal methods for the design of product synthesis pathway.