Combinatorial design and assembly for engineering multi-gene pathways and processes

Abstract: Bacterial gene clusters encode diverse cellular functions, including energy utilization, nanomaterials, and natural products for medicine and agriculture. Genetically manipulating systems of this size is slow, difficult, and complicated by complex and overlapping native genetics. Refactoring is a strategy to re-write the genetics of these large gene clusters to make them easier to engineer. Our group couples genetic refactoring with recent DNA synthesis and assembly technologies to better understand and engineer multi-gene biological functions and processes. Here, I will briefly describe efforts to optimize the genetics of a model synthetic nitrogen fixation gene cluster and discuss recent progress on applying this paradigm for natural product discovery and engineering.