CBE Seminar (Zoom): Synthetic Biology Approach to Discover New Bioactive Molecules

Registration Link: https://forms.gle/ehqdSVrpVeNF9ocX8

Abstract: For decades, fungi have been an important source of medically relevant natural products (NPs). Recent advances in DNA sequencing have revealed that the biosynthetic potential of fungal genomes is much deeper than previously realized. Difficulties in culturing and genetically engineering many fungi, combined with the fact that many NP biosynthetic gene clusters (BGCs) are not expressed under standard laboratory conditions, result in much of this biosynthetic potential remaining untapped. Here we describe the realization of a pipeline based in S. cerevisiae encompassing bioinformatic tools for BGC curation, genetic parts for BGC refactoring and improved DNA assembly for BGC building. With this pipeline, we have successfully detected novel NPs from several previously unstudied fungal BGCs and have structurally characterized a subset of the BGC-associated compounds. We also developed activity-guided methods to discover natural products of new function and validated the biological activity using higher-order model systems. Our pipeline demonstrates how high-throughput synthetic biology tools can facilitate the rapid discovery of complex chemical scaffolds of potential pharmaceutical relevance and their production in model fungal hosts.

Bio: Yi Tang received his undergraduate degree in chemical engineering and material science from Penn State University. He received his Ph.D. in chemical engineering from California Institute of Technology under the guidance of David A. Tirrell. After NIH postdoctoral training in chemical biology from Chaitan Khosla at Stanford University, Tang started his independent career at UCLA in 2004. He is currently a professor at the Department of Chemical and Biomolecular Engineering at UCLA, and holds joint appointments in the Department of Chemistry and Biochemistry; and Department of Bioengineering. His awards include the ACS Arthur C. Cope Scholar Award (2012), the EPA Presidential Green Chemistry Challenge Award (2012), NIH DP1 Director Pioneer Award (2012) and the ACS Eli Lilly Award in Biological Chemistry (2014). 

Host: Assistant Professor Han Li