S86: Multivariate-modular metabolic engineering for optimizing chemical biosynthesis in Escherichia coli

Natural product biochemicals are primarily extracted from plants in low yield, and there has been immense interest in developing cost-competitive biotechnological production of these chemicals due to limited raw material accessibility, low yields and high costs of the plant extraction process or chemical synthesis. Recently, we developed a new metabolic engineering approach, multivariate modular metabolic engineering (MMME), and a platform bacterial system capable of overproducing the terpenoid precursor of several hundred chemicals used in everyday life. We have demonstrated the application of our approach to engineer diterpenoid taxadiene, hydroxylated taxanes, levopimaradiene and kaurene production in E. coli. MMME enabled the systematic assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as modules. We have extended our approach up to three modules and established that fine balance in the pathway enzyme expression is key to the high level production of these molecules. Here, we focus on the development of MMME and its application to production of complex terpenoids.