Asher Hollenbeak

Research: Directed Evolution of Antibiotic Biosynthetic Pathways

In the antibiotic discovery process, natural products are oftentimes too large or complicated to be chemically modified without disruption of chemical properties, as is the case in everninomicin, a large oligosaccharide antibiotic synthesized via a 130 step biosynthesis. This prevents the facile generation of natural product analogs in a laboratory setting. My project involves the modification of a known antibiotic, everninomicin, via directed evolution of the proteins in the biosynthetic pathway. The generation of everninomicin analogs will precede the testing of everninomicin analogs for ribosomal binding affinity and increased antibiotic activity towards Gram negative bacteria. This will be the first time a new antibiotic will be synthesized through directed evolution of the biosynthetic pathway.

Mentor: Brian Bachmann, Ph.D.