In the hunt for improved antibiotics, it is important to realize that natural products have been, without question, the most prolific source of all medicines. With the advent of massively parallel DNA sequencing, it has become apparent that our knowledge of natural product structure and function is astonishingly incomplete. Exploration of uncharted natural product chemical space will undoubtedly lead to improved, and entirely new, medicines. Thus, our group focuses on elucidating the biosynthesis, structure, and function of natural products. The system we focus on is the thiazole/oxazole-modified microcins (TOMMs). Characterized TOMMs have activities ranging from antibacterials to virulence-promoting toxins. Therefore, the study of TOMMs allows us to not only better understand bacterial virulence (where pharmacological intervention would constitute a pathogen-specific approach to bacterial infection) but also explore unique chemical architectures, ideally positioning us to introduce new structural classes of antibiotics.This talk will focus on our recent work on a TOMM natural product known as plantazolicin. Discovered in 2011, this polyheterocyclic compound boasts a remarkable selectivity for Bacillus anthracis, the causative agent of anthrax. Through chemical synthesis, derivatization, and biosynthetic engineering, we have generated many analogs of PZN to ascertain information about its structure-activity relationships and unique mode-of-action.

Chemical approaches to suppress the rise of antibiotic drug resistance

248th National Meeting (2014)

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