Often the pharmaceutical potential of natural product scaffolds is underexplored due to the difficulty in accessing analogs to complex secondary metabolites using traditional synthetic methods. Recent advances in sequencing technology have facilitated the identification of secondary metabolite gene clusters from genomic and metagenomic samples, which has led to an explosion of newly identified and annotated secondary metabolite pathways.
In the Narayan Lab, we leverage the powerful reactivity and selectivity of enzymes from natural product pathways in concise approaches to natural products and their analogs. Projects are initiated with the identification of an enzyme with synthetic potential unmatched by chemocatalytic methods and continue by demonstrating the substrate scope and potential applications of the biocatalyst including the synthesis of biologically active molecules. Synthetic efforts feed biological studies on activity, which inform the subsequent selection of synthetic targets.
In the News
- Enzymes trapped and zapped for use outside cells, Nature, Mar. 21
- Revealing how enzymes turn a toxin into a potential painkiller, Chemical & Engineering News, Apr. 23
- Charting a Course for Chemistry, Nature Chemistry, Mar. 22
- Enzyme redesign magnifies rare sugar synthesis, Chemistry World, May 1
- How bacteria build a deadly toxin, Nature, Feb. 19
- Mixture of liver enzymes improve drug leads, Chemical & Engineering News, April 17
- A year in the life of a new professor, Chemical & Engineering News, May 17
- Chemists conquer oxidative dearomatization with trio of enzymes, Chemical & Engineering News, Nov. 17
- Named one of Chemical & Engineering News' Talented 12
"Although enzymes that catalyse transformations in the biosynthesis of natural products often demonstrate remarkable activity and selectivity, there are typically challenges — usually relating to substrate scope and stability — that must be overcome before they can be used effectively in the laboratory by synthetic chemists. Now, a team led by Alison Narayan has shown how three related enzymes that are known to catalyse the oxidative dearomatization of phenols and resorcinols can be used to make ortho-quinol products (an example of which is depicted on the cover) with impressive site- and stereoselectivity. The method is robust enough to be scaled-up to gram-scale reactions and its use in multi-enzyme and chemoenzymatic cascades has also been demonstrated."