Engineering Regulatory Networks for Natural Product Discovery​

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Bacterial natural products are produced in response to a variety of internal and external stimuli, but in the lab, it is challenging to induce their production (0 to 1) or overproduction (1 to 100). We utilize synthetic biology and protein engineering to rewire global regulatory networks to 'trick' the bacteria into producing the compounds we want. In addition to the translational applications of the natural products and their biosynthetic enzymes, this project aims to apply our findings to the fundamental understanding of regulators and their networks.

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Synthetic Biology for Biosynthetic Gene Cluster Activation

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Mining the genomes of bacteria has revealed dozens of BGCs per strain, but some BGCs stand out more than others due to the predicted bioactivities or structural novelties of their encoded natural products. To access these natural products, we employ synthetic biology tools, such as CRISPR-Cas9, to directly target and activate their BGCs. 

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Unlocking Novel Chemistry with Natural Product Enzymology

 

As new natural products are identified, there will inevitably be novel enzymology that is associated with the biosynthesis of these complex and valuable compounds. A combination of in vivo, in vivo, computational, and structural biology studies will be performed for enzymes that have potential to unlock new chemistry or improved fundamental understanding of known enzyme classes.