Abstract
Systems metabolic engineering is facilitating the development of high-performing microbial cell factories for producing chemicals and materials. However, constructing an efficient microbial cell factory still requires exploring and selecting various host strains, as well as identifying the best-suited metabolic engineering strategies, which demand significant time, effort, and costs. Here, we comprehensively evaluate the capacities of various microbial cell factories and propose strategies for systems metabolic engineering steps, including host strain selection, metabolic pathway reconstruction, and metabolic flux optimization. We analyze the metabolic capacities of five representative industrial microorganisms as cell factories for the production of 235 different bio-based chemicals and suggest the most suitable host strain for the corresponding chemical production. To improve the innate metabolic capacity by constructing more efficient metabolic pathways, heterologous metabolic reactions, and cofactor exchanges are systematically analyzed. Additionally, we present metabolic engineering strategies, which include up- and down-regulation target reactions, for the improved production of chemicals. Altogether, this study will serve as a comprehensive resource for the systems metabolic engineering of microorganisms in the bio-based production of chemicals.