Research: Colloquia Review

"Exploitation of Nature's Chemist"

The Sherman lab is pursuing the discovery and study of natural products generated by diverse marine and terrestrial microorganisms (e.g. cyanobacteria, actinomycetes). These potential drugs are synthesized through biosynthetic pathways referred to as secondary metabolism. Understanding the pathways that produce a natural product (like cryptophycins, illustrated below) increases our ability to manipulate the system and enables synthesis of the natural product and novel derivatives with enhanced therapeutic potential.

Cryptophycin has great clinical potential as a tubulin-binding anti-cancer agent. We have recently characterized the genetic blueprint comprising the cryptophycin biosynthetic pathway from the cyanobacterium Nostoc sp. ATCC 53789. Nostoc sp. ATCC 53789 is a cyanobiont (lichen symbiont) isolated from a lichen on Aaron Island, Scotland.

Drs. Zach Beck and Courtney Aldrich of the Sherman lab have used a combination of chemical synthesis and the thioesterase enzyme from the biosynthetic pathway to engineer naturally produced cryptophycins and derivatives. This novel and highly efficient approach to the synthesis of cryptophycins will enable effective production of large libraries of compounds that can be screened for improved pharmacological properties. In addition, these studies contribute to a better understanding of the enzymes that have evolved in nature to produce these important molecules.

—Zachary Q. Beck, Ph.D., Sherman Laboratory, April 2005