Synthetic Biochemistry: The Bio-inspired Cell-Free Approach to Commodity Chemical Production

• Published in: Trends in biotechnology (Regular ed.) 2020-07, Vol.38 (7), p.766-778
• Main Authors: Bowie, James U., Sherkhanov, Saken, Korman, Tyler P., Valliere, Meaghan A., Opgenorth, Paul H., Liu, Hongjiang
• Format: Article
• Language: English
• Subjects: Biochemistry; biofuel; biomanufacturing; Biomass; cascade biocatalysis; Chemicals; Commodities; commodity chemical; Engineering; Enzymatic activity; enzyme cascade; Enzymes; Ethanol; Flexibility; green chemistry; Metabolic engineering; Metabolism; multienzyme systems; Natural products; Optimization; Organisms; Production methods; Productivity
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/j.tibtech.2019.12.024

Metabolic engineering efforts that harness living organisms to produce natural products and other useful chemicals face inherent difficulties because the maintenance of life processes often runs counter to our desire to maximize important production metrics. These challenges are particularly problematic for commodity chemical manufacturing where cost is critical. A cell-free approach, where biochemical pathways are built by mixing desired enzyme activities outside of cells, can obviate problems associated with cell-based methods. Yet supplanting cell-based methods of chemical production will require the creation of self-sustaining, continuously operating systems where input biomass is converted into desired products at high yields, productivities, and titers. We call the field of designing and implementing reliable and efficient enzyme systems that replace cellular metabolism, synthetic biochemistry. Cost-effective production of chemicals in engineered organisms is challenging because there is a basic conflict between the needs of the cell for life, and our needs for commercial viability.The synthetic biochemistry approach can free us from cellular limitations, opening up new possibilities for enhancing biobased chemical production parameters.Cost-effective cell-free bioreactor construction requires designing simple, robust systems that can run efficiently for long periods of time. While considerable challenges remain before biomanufacturing is possible at the scale currently used in microbial systems, recent progress suggests that a cell-free approach has promise.