High-throughput screening for high-efficiency small-molecule biosynthesis

Systems metabolic engineering faces the formidable task of rewiring microbial metabolism to cost-effectively generate high-value molecules from a variety of inexpensive feedstocks for many different applications. Because these cellular systems are still too complex to model accurately, vast collections of engineered organism variants must be systematically created and evaluated through an enormous trial-and-error process in order to identify a manufacturing-ready strain. The high-throughput screening of strains to optimize their scalable manufacturing potential requires execution of many carefully controlled, parallel, miniature fermentations, followed by high-precision analysis of the resulting complex mixtures. This review discusses strategies for the design of high-throughput, small-scale fermentation models to predict improved strain performance at large commercial scale. Established and promising approaches from industrial and academic groups are presented for both cell culture and analysis, with primary focus on microplateand microfluidics-based screening systems.

Automated summary

Systems metabolic engineering is a challenging task that involves rewiring microbial metabolism to generate high-value molecules from inexpensive feedstocks. High-throughput screening of engineered organism variants for scalable manufacturing potential is necessary, requiring carefully controlled, parallel fermentations and precise analysis of complex mixtures. Strategies to design high-throughput, small-scale fermentation models for predicting improved strain performance at large commercial scale, including microplate and microfluidics-based screening systems, are essential for success.