Synthetic Biology Approach to Scaffolding Pathways for Small Molecule Biosynthesis
Two classes of compound dominate the modern drug landscape: natural products and monoclonal antibodies (mAbs). Together these comprise close to 70% of approved drugs in the U.S. and Europe. mAbs have a distinct advantage because they can be rapidly evolved by directed evolution to have exquisitely high affinity for their drug target. Yet mAbs are limited due to their size, which effects cell penetrance and bioavailability: they can only access a subset of therapeutic targets. In contrast, natural products are significantly more challenging to manipulate than mAbs, but they possess privileged scaffolds, designed by nature to access a host of intercellular targets. We describe efforts to combine directed evolution with natural product biosynthetic pathways to evolve new natural product-like scaffolds and thereby accelerate the discovery of new therapeutics.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.