Integration of molecular biology and automation to create HTP genetic design libraries for industrial strain improvement

Industrial fermentation by bacteria and fungi can be utilized to convert simple sugars to enzymes, pharmaceuticals, organic acids and other valuable commercial products. The efficiency in which microbes can be used to generate these products has a direct impact on cost of production and therefore strain improvement is routinely sought. Traditional strain improvement programs utilize random mutagenesis and screening to identify strains with improved characteristics. This “classical” mutagenesis approach has been used to obtain improved strains with desired phenotypes such as higher titer, yield, and productivity, as well as other valuable tolerance characteristics (i.e. heat, pH, product toxicity etc.). However, mutagenesis campaigns also accumulate deleterious changes and are limited in their ability to provide improvements in multiple traits simultaneously. To address this problem, Zymergen has built a platform for automated and high-throughput strain engineering that is focused on improving the economics of large-scale fermentation processes. This is done by generating a comprehensive library of genetic changes that is applied to production strains and systematically screened for improvements in multiple traits of interest. Genetic changes associated with desired phenotypic outcomes are then combined to generate a strain with improved fermentation characteristics. Zymergen has successfully deployed these methods for large scale industrial production hosts that have demonstrated superior performance at scale.