From Industrial By-Products To Value-Added Compounds: The Design Of Efficient Microbial Cell Factories By Coupling Systems Metabolic Engineering And Bioprocesses

Microbial cell factories have been used for the production of valuable chemical compounds using a classical metabolic engineering approach, but this requires much time and cost, and labor-intensive processes to make cell factories industrially competitive. Systems metabolic engineering is an upgraded version, which understands the cell as a complex system in which networks of genes, transcripts, proteins, and metabolites are connected, facilitating the analysis of potential cell factories. However, efficient cell factory design, which aims for industrial-scale production, requires a comprehensive system, which goes beyond metabolism and considers industrial production challenges. A review is provided here of the developments and challenges in the application of systems biology for metabolic engineering and in recovery and purification processes for scaling up bio-based chemical production. Then, a new design, build, test, and learn prediction cycle for metabolic engineering is proposed, for the design of efficient cell factories. This considers system-wide characteristics and relies upon the integration of upstream (strain development), midstream (fermentation), and downstream (recovery and purification) analysis for strain design. In addition to this cycle, three issues should be taken into consideration: (i) The use of simple, available, and inexpensive materials; (ii) the identification and elimination of bottlenecks using non-complex recovery and purification processes; (iii) the assessment of commercial and chemical industry requirements from the perspective of system efficiency. In this context, highly efficient microbial cell factories should be developed to produce compounds with improved production performance to meet industrial application requirements. (c) 2020 Society of Chemical Industry and John Wiley & Sons, Ltd