Tools and strategies of systems metabolic engineering for the development of microbial cell factories for chemical production

Abstract

This tutorial review covers tools, strategies, and procedures of systems metabolic engineering facilitating the development of microbial cell factories efficiently producing chemicals and materials.

Metabolic Engineering for Glycyrrhetinic Acid Production in Saccharomyces cerevisiae

“…The artificially constructed cell factories need to be continuously optimized through the Design-Build-Test-Learn (DBTL) cycle (Nielsen and Keasling, 2016). The DBTL cycle includes new enzyme discovery, heterologous gene expression, promoter engineering, metabolic flux balance, pathway optimization, oxidation and reduction system balance, genome-scale metabolic models and other metabolic engineering strategies (Jiang et al, 2020;Ko et al, 2020;Tang et al, 2020;Wang M. et al, 2020). Finally, a high-yield GA or other natural product microbial cell factory can be obtained.…”

Advances in Metabolic Engineering of Saccharomyces cerevisiae for Cocoa Butter Equivalent Production

“…The identified efficient/potential genes can then be used for further metabolic engineering or synthetic biology modification of S. cerevisiae. During the typical metabolic engineering cycle of Design-Build-Test-Learn (DBTL), lipid biosynthetic pathway can be redesigned and rewired (Nielsen and Keasling, 2016;Ko et al, 2020; Figure 2C). The designed pathway can be further built with advanced synthetic biology and systems biology tools to generate strains with high-level CBE production.…”

“…The designed pathway can be further built with advanced synthetic biology and systems biology tools to generate strains with high-level CBE production. When the TAG/CBE titer, rate and yield (TRY) of the engineered strains are high enough, they will be used for further large-scale fermentation; if the TRY are low, novel engineering strategies should be used for next round strain optimization until high TRY are obtained (Nielsen and Keasling, 2016;Ko et al, 2020).…”

The Bipartisan Future of Synthetic Chemistry and Synthetic Biology

“…Synthetic biology in particular has gained significant traction, not least due to its ability to use waste and renewable feedstocks for the production of chemicals and pharmaceuticals. [3][4][5][6] Yet synthetic biology is inherently limited by the reactions known to nature, precluding its ability to access vast swathes of chemical space. Forecasts estimate that only about 20 % of the chemical industry can be replaced by bio-based alternatives, with processes such as metathesis and cross-coupling currently reliant on chemical approaches.…”