Prospects of microbial cell factories developed through systems metabolic engineering

Abstract

While academic-level studies on metabolic engineering of microorganisms for production of chemicals and fuels are ever growing, a significantly lower number of such production processes have reached commercial-scale. In this work, we review the challenges associated with moving from laboratory-scale demonstration of microbial chemical or fuel production to actual commercialization, focusing on key requirements on the production organism that need to be considered during the metabolic engineering process. Metabolic engineering strategies should take into account techno-economic factors such as the choice of feedstock, the product yield, productivity and titre, and the cost effectiveness of midstream and downstream processes. Also, it is important to develop an industrial strain through metabolic engineering for pathway construction and flux optimization together with increasing tolerance to products and inhibitors present in the feedstock, and ensuring genetic stability and strain robustness under actual fermentation conditions.

Figure 1

Overview of the microbial cell factory design process. For successful commercial implementation, the full picture should be considered throughout the design process. A. Considerations relating to the choice of renewable feedstock, including the location of the production facility in close proximity to the available feedstocks, as indicated by blue (correct) and red (incorrect) concentric circles. B. The metabolic engineering process, starting from selection of production organisms and iterating through design‐build‐test‐learn cycles until the process requirements are met. C and D. Critical parameters for the production process and downstream purification to final products respectively.