High-throughput strain engineering tools to access natural product biodiversity

The molecular diversity of the natural products world is unparalleled in its rich array of functional groups, and wide application space. Optimization of microbial production of any target natural product however, requires repeated iterations of the design-build-test-Learn (D-B-T-L) engineering cycle. The rate at which any team can execute the D-B-T-L engineering cycle directly affects the development time for any natural product. At Amyris, we have built the Automated Strain Engineering (ASE) and High-Throughput Screening (HTS) pipelines that rapidly accelerate the D-B-T-L cycle at a high-throughput scale using cutting edge synthetic biology tools. With these capabilities, scientists at Amyris can probe multiple natural product pathways simultaneously, speeding the cycle of strain improvement and parallel investigation of multiple solution sets. Development of these platforms was however a massive undertaking, which required collaborations across multiple disciplines and breaking down the most miniscule strain engineering steps into protocols that could be controlled by software programs and automation scripts. This presentation will cover details of the automated platforms that enabled Amyris scientists to rapidly iterate through multiple D-B-T-L cycles of the strain engineering process, as well as the engineering of metabolic pathways to convert naïve yeast strains into commercial scale production hosts for various natural products.