NSF Award
1608723
With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Christopher Calderone from Carleton College. Small molecules, produced by microbial cells and known as non-ribosomal peptides are the source of dozens of clinically useful medicines, including antibiotics and anticancer drugs. The structures of these molecules is incredibly complex and diverse, but they are all produced by "assembly lines" that are made up of only a handful of different types of repeating biological machinery. This research is identifying new types of biological assembly line machinery that can explain the origins of a large number of non-ribosomal peptides and ultimately allow the design of new varieties that are not currently accessible. The new varieties could have valuable therapeutic potential. An additional important component of this project is the development of the LearningWorks program in downtown Minneapolis to teach underserved middle-school students molecular biology concepts and techniques. <br/><br/>This research is aimed at characterizing a predicted subclass of condensation domains involved in non-ribosomal peptide biosynthesis. Though non-ribosomal peptide synthetases have been extensively studied over the past decades, mechanistic reasoning and bioinformatic analysis suggests that there is a broadly distributed, but as-yet uncharacterized, subclass of the condensation domain involved that is able to catalyze dehydration in addition to canonical amide-bond formation. These experiments are aimed at reconstituting the biosynthetic pathway from Pseudomonas aeruginosa that leads to aminomethoxy-trans-butenoic acid (AMB) in vitro, the centerpiece of which is a predicted condensation domain-catalyzed dehydration. In addition, this funding supports the development of educational modules for incorporation into the undergraduate teaching lab and the curriculum of LearningWorks, a public-private partnership in downtown Minneapolis that serves middle-school students from underserved populations.
