Chemistry and Biochemstry Dept. Seminar: Dr. Nathan Schnarr, UMass Amherst
|Category:||College Of Arts And Sciences|
|Date & Time:||
from 04:00 PM to 05:30 PM
|Sponsored by:||Chemistry & Biochemistry Deptartment|
Dr. Sivappa Rasapalli
TITLE: Simplified Approaches for Improved Control Over Polyketide Engineering
The steady rise of drug-resistant bacteria coupled with decreasing numbers of viable therapeutics in the pharmaceutical pipeline underscores the need for novel strategies focused on rational exploration of chemical space to design and identify the next generation of antibiotics. Polyketides and non-ribosomal peptides make up an enormous class of natural products whose unique biosynthetic assemblies provide great potential for engineered product variation in well-defined chemical scaffolds. Unfortunately, most attempts to generate new biologically active analogs of these molecules have suffered from poor yields largely due to inherent specificity within the enzymes responsible for their production. Using an array of chemical and biological tools, our research focuses on understanding recognition motifs leading to this selectivity to potentially improve engineering efforts at both the genetic and molecular levels. In addition, we are developing small-molecule probes designed to interrogate all steps of polyketide biosynthesis. Using small, reactive heterocycles as electrophilic partners for a key component of all polyketide synthases, we have developed fluorescence-based strategies for monitoring the behavior of enzymes associated with elongation and tailoring of polyketide intermediates.