Motivated by Knowledge. Inspired by Nature. Excited by Discovery.
Microbial Natural Products
Small molecules are often left out in the central dogma of biology, as Stuart Schreiber described. Natural products are the most chemically and structurally diverse naturally-occurring small molecules, have diverse roles in nature, and are the most successful class of compounds in the clinic. The actinomycetes are prevalent producers of natural products and genome sequencing and bioinformatics reveals there are countless natural products waiting to be discovered. I am interested in the discovery of microbial natural products and their applications in human health.
Terpenoid Discovery and Biosynthesis
According to the Dictionary of Natural Products, there are >70,000 known terpenoids. There are only 272 terpenoids from actinobacteria (<0.4%)! Is this extreme discrepancy due to lack of terpenoid production, lack of scientific focus in this field, or lack of efficient means of terpenoid discovery in bacteria? Recent genomics studies suggest actinobacteria have the biosynthetic potential for terpenoid production. Given my background in terpene enzymology and diterpenoid natural products, I am equipped to use a multidisciplinary approach to understand this discrepancy, discover novel bacterial terpenoids, and reveal how bacteria utilize terpenoids to create structural diversity in natural products.
The tremendous structural diversity in natural products requires diversity in the enzymes that construct and functionalize these scaffolds. This includes sequence, structural, and functional diversity. The discovery and study of enzymes from natural products biosynthetic pathways has created biochemical, structural, and mechanistic paradigms in enzymology, while exposing their potential for biomedical and biotechnological applications. What has Nature evolved to do that we haven't discovered yet?