Synthetic Biology Platforms for Natural Product Biosynthesis and Discovery

Plants are a rich source of unique scaffolds, including 25% of natural-product-derived drugs. However, the discovery, synthesis, and overall material supply chains for sourcing plant natural products and their derivatives remain ad hoc, biased, and tedious. While microbial biosynthesis presents compelling alternatives to traditional approaches based on extraction from natural plant hosts, many challenges exist in the reconstruction of plant specialized metabolic pathways in microbial hosts. My laboratory has developed novel synthetic biology approaches for complex biosynthesis processes, including geneticallyencoded biosensors to support noninvasive detection of key pathway metabolites and spatial engineering strategies to direct the activities and specificities of pathway enzymes. We have utilized these strategies to develop yeast-based production platforms for an important class of plant alkaloids, the benzylisoquinoline alkaloids. These synthetic biology platforms will lead to transformative advances in natural product discovery, drug development, and production.