The lab has developed several technologies to study secondary metabolites producing pathways and their producer organisms. Our area of focus is the protein-protein interactions (PPIs) of fatty acid synthases (FASs), polyketide synthases (PKSs), and non-ribosomal peptide synthases (NRPSs). Learn more
Recently, the spliceosome has garnered much attention due to its implication in many cancers. The lab has developed medicinal chemistry and chemical biology program in efforts to bring new therapeutics into the clinic as well as to probe the mechanistic undertones of how splicing is affected and altered. Learn more
Algae have emerged as an attractive feedstock for the mass production of the renewable source due to their fast growth rate, and flexible habitat preferences. The potential of algae biotechnology is the most promising for green materials to produce polymers such as polyurethane, polyhydroxyurethanes and polyester. Learn more
Our group is involved in the fundamental understanding of carrier protein biosynthetic pathways, which includes non-ribosomal peptide, polyketide, and fatty acid biosynthesis. These pathways all require the participation of a carrier protein (CP), a small four-helix bundle protein that covalently tethers all substrates and intermediates. CPs play an active role, interacting with both tethered substrates and partner enzymes. We have developed unique molecular tools to trap, visualize, and modify these protein•protein and protein•substrate interactions. Through the complimentary and collaborative application of chemical, structural, and computational biology, we are beginning to understand the complexities of CP-dependent biosynthesis. These discoveries also inform the future direction of these pathways for the development of next-generation therapeutics, biofuels, and fine chemicals through synthetic biology.
We are also involved in several areas of drug discovery, with an emphasis on anticancer and antibiotic natural products. Using methods that include organic synthesis, medicinal chemistry, and synthetic biology, we aim to discover and develop new therapies that address critical needs. One of the most advanced projects in the lab is our discovery and development of spliceosome modulators. The spliceosome has recently been identified as a promising target for the design of next generation cancer therapeutics, and we have discovered new analogs of the polyketide natural products pladienolide B and FD-895 that selectively target cancer cells at sub-nanomolar levels. In addition, we are using these modulators as chemical biology tools to understand both spliceosome activity as well as the selectivity inherent in these compounds.
As major participants in the California Center for Algae Biotechnology, our lab has been among the teams funded by the US DOE to develop biofuels from algae. More recently, we have turned to renewable materials as an alternative to petrochemicals. With other labs at UC San Diego, we developed polyurethane formulations for both rigid and flexible forms that are sustainably sourced and that biodegrade at the end of their useful life. To date, we have applied these technologies to the fabrication of algae surfboards and flip-flops. We are continuing to advance both the material science and process chemistry, with the aspiration to reach 100% renewable content while still maintaining biodegradability and meet specifications for material performance.
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