Harnessing natural product biosynthetic machinery

Cladoniamide, a new alkaloid originally isolated from a bacterial strain found on the surface of a British Columbia lichen, has attracted attention as a potential new colorectal cancer drug.

The objective of this proposal is to harness the cladoniamide biosynthetic pathway to produce cladoniamide and new derivatives at high levels and generate new “hybrid” compounds by genetic manipulation of cladoniamide and related indolocarbazole biosynthetic pathway

This proposal aims to use biological and chemical tools to access new therapeutic molecules, specifically targeting colon cancer. The approach uses biosynthetic machinery from microorganisms to make complex natural products and their “unnatural” derivatives. Dr. Du will develop engineered biological platforms for the production of molecules that cannot be acquired in sufficient quantities through either organic synthesis or cultivation of a natural producer.

This project represents a unique approach that combines genomic and chemical tools to develop new drug leads from the cladoniamide scaffold. Results from this work will lay the groundwork for future, collaborative efforts in drug research, development, formulation, testing and commercialization.