Department of Chemistry, Seoul National University
RiPPs
(Ribosomally synthesized and Post-translationally modified Peptides)
: Genome mining, Structure, Mechanism
Using approaches in molecular biology, bioinformatics, enzymology, and structural biology, one research program aims at expanding the natural scope of a class of natural products, ribosomally-synthesized and post-translationally modified peptides (RiPPs), and dissecting the biosynthetic pathway and mechanism. In contrast to non-ribosomal peptides and polyketides, whose biosynthetic gene clusters (BGCs) encode several common enzymes and thus can be easily identified in the sequenced genome, RiPPs are synthesized by a much diverse set of primary modification enzymes. Therefore, it is still unknown how many novel classes of RiPPs that differ in their central structures and biosynthetic enzymes exist in nature. This research currently focuses on multicyclic peptides with ester/amide crosslinks (OEPs or graspetides), but will be expanded to other classes of RiPPs.
Targeted in vivo mutagenesis
:Continuous directed evolution
Another research program is to develop a new approach of directed evolution of proteins. By mimicking the process of the natural protein evolution, in which DNA diversification and clonal selection are the central processes, directed evolution allows to obtain in laboratory protein variants that have better properties. However, traditional directed evolution relies on in vitro DNA diversification, and thus is limited by labor-intensive discrete steps and relatively low size of DNA library. The in vivo mutagenesis methods that have been recently reported greatly facilitate the continuous directed evolution, in which the gene diversification and selection are simultaneously performed inside cells. However, the simple and fast in vivo mutagenesis methods with better targeting abilities (e.g. target only desired genes) are yet to be developed. This research aims at developing novel in vivo mutagenesis methods with high target-specificity and applying them to the evolution of enzymes of practical value. These studies will ultimately help to explore novel structural and functional space of biomolecules with implications in biotechnology and medicine.