(142g) Biology By Design: Emerging Tools in Cell-Free Synthetic Biology

Imagine a world in which we could adapt biology to manufacture any therapeutic, material, or chemical from renewable resources, both quickly and on demand. Industrial biotechnology is one of the most attractive approaches for addressing this need, particularly when large-scale chemical synthesis is untenable. Unfortunately, current approaches to engineering organisms remain costly and slow. This is because cells themselves impose limitations on biobased product synthesis. It is difficult to balance intracellular fluxes to optimally satisfy a very active synthetic pathway while the machinery of the cell is functioning to maintain reproductive viability. Further, chemical reactions take place behind a selective barrier, the cell wall, which limits sample acquisition, monitoring, and direct control. In addition, cells are adapted to a relatively simple chemical operating system (i.e., a few common sugars, 20 amino acids), which presents researchers a limited set of accessible molecules with which to work. In this presentation, I will discuss my group's efforts to overcome these limitations and widen the aperture of the traditional model of biotechnology. In one direction, we seek to create a new cell-free framework that enables systematic optimization and debugging of biosynthetic pathways for metabolic engineering. In another area, we are catalyzing new directions for the synthesis of homogeneous glycoprotein therapeutics and vaccines. Our new paradigms for biochemical engineering are enabling a deeper understanding of why nature’s designs work the way they do, as well as opening the way to novel biobased products that have been impractical, if not impossible, to produce by other means.