Specialized metabolites represent a class of compounds with unique and complex chemistries and which possess a myriad of commercial applications, from pharmaceuticals and food products to industrial chemicals. Despite their intrinsic value, however, sourcing remains a bottleneck to more widespread use due to their low abundance in nature and the inherent difficulties in applying metabolic engineering and industrial biotechnology approaches to produce these complex natural chemistries in microbial hosts. At Manus Bio, we focus on addressing the challenges of microbial fermentation of plant secondary metabolites through the combined application of our proprietary Multivariate Modular Metabolic Engineering (MMME) and Pathway Integrated Protein Engineering (PIPE) technologies for optimizing heterologous enzymes and pathways. With this approach, we have successfully demonstrated the potential of using a single microbe to catalyze several complex chemical reactions, including polymerization, cyclization, multiple oxidations, and up to six glycosylations, all while producing the target metabolite at greater than 95% purity. In this presentation, we will highlight some of the important insights and guiding principles used to engineer complex biochemical pathways in simple bacterial systems, such as Escherichia coli.
