Bacteria live a rich metabolic life. They have remarkable abilities to synthesize small molecules with intriguing chemical structures and potent biological activities. These small molecules, or natural products, have been widely used as life-saving pharmaceuticals such as antibiotics and tools to understand biology. Much of the bacterial small molecules remain unexplored and consequently underutilized. This talk will discuss our work on understanding the chemistry in the biosynthesis and mode of action of antibiotics, as well as mining bacterial genomes for new bioactive small molecules. Using a combination of chemistry, bacterial genetics, and systems biology tools, we identified a new mode of action for natural products called dithiolopyrrolones. These compounds exert their broad-spectrum activity by chelating metal ions in the cell and inhibiting the activity of metalloenzymes. This mechanism may be explored to control multidrug-resistant bacterial infections.

Mighty chemistry of bacterial small molecules

255th National Meeting (2018)

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