Terpenoid Discovery and Biosynthesis
According to the
Dictionary of Natural Products, there are >80,000 known terpenoids.
There are only <1,500 terpenoids from all bacteria; <700 from actinobacteria! 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. Recent biochemical studies have revealed that terpene synthases are much more diverse than the canonical superfamily of enzymes. We are 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.
Microbial Natural Products
Small molecules are often left out in the central dogma of biology. Natural products (NPs) 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. We are interested in the discovery of bacterial NPs and their applications in human health.
Why use bacteria to discover natural products?
1. Workhorses: Actinomycetes, a family of Gram-positive bacteria, are the workhorse producers of NPs. Most antibiotics currently used today are either from actinomycetes or derived from actinomycete antibiotics.
2. Biosynthetic Potential: Actinomycete genomes are large. Large regions of their genomes encode NPs, most of which are uncharacterized and novel.
3. Gene Clusters: The genes encoding NP biosynthetic enzymes are (commonly) clustered together, simplifying NP discovery, elucidation of biosynthetic and self-resistant mechanisms, and revealing new enzymes and enzyme functions.
4. Facile genetics: Feasible genetic tools are available for many of the actinomycetes, providing opportunities for biosynthetic and engineering studies.
5. Renewable and Repeatable: Bacteria are a renewable resource; you don't have to cut down trees, collect animals, or worry about finding the same resource again. The production of NPs is also repeatable, facilitating isolation and optimization of production yields.
