van Rosmalen R P, Moreno-Paz S, Duman-Özdamar Z E, Suarez-Diez M
Laboratory of Systems and Synthetic Biology, Stippeneng 4 6708 WE Wageningen, the Netherlands.
Metab Eng Commun. 2024 Jun 24;19:e00244. doi: 10.1016/j.mec.2024.e00244. eCollection 2024 Dec.
Genome-scale metabolic models of microbial metabolism have extensively been used to guide the design of microbial cell factories, still, many of the available strain design algorithms often fail to produce a reduced list of targets for improved performance that can be implemented and validated in a step-wise manner. We present Comparative Flux Sampling Analysis (CFSA), a strain design method based on the extensive comparison of complete metabolic spaces corresponding to maximal or near-maximal growth and production phenotypes. The comparison is complemented by statistical analysis to identify reactions with altered flux that are suggested as targets for genetic interventions including up-regulations, down-regulations and gene deletions. We applied CFSA to the production of lipids by and naringenin by identifying engineering targets in agreement with previous studies as well as new interventions. CFSA is an easy-to-use, robust method that suggests potential metabolic engineering targets for growth-uncoupled production that can be applied to the design of microbial cell factories.
微生物代谢的基因组规模代谢模型已被广泛用于指导微生物细胞工厂的设计，然而，许多现有的菌株设计算法往往无法生成一份可逐步实施和验证的、用于提高性能的精简靶点列表。我们提出了比较通量采样分析（CFSA），这是一种基于对对应最大或接近最大生长及生产表型的完整代谢空间进行广泛比较的菌株设计方法。通过统计分析对该比较进行补充，以识别通量发生改变的反应，这些反应被建议作为基因干预的靶点，包括上调、下调和基因缺失。我们将CFSA应用于 生产脂质以及 生产柚皮素，确定了与先前研究一致的工程靶点以及新的干预措施。CFSA是一种易于使用、稳健的方法，它为非生长偶联型生产提出了潜在的代谢工程靶点，可应用于微生物细胞工厂的设计。
