Using Chemical Knowledge to Uncover New Biological Function: Discovery of the Cylindrocyclophane Biosynthetic Pathway.

An understanding of organic chemistry can play a central role in uncovering enzymes with new biochemical functions. We have recently identified the enzymes involved in the biosynthesis of the cylindrocyclophanes, a structurally unique family of natural products, and found that this pathway employs a remarkable macrocyclization event that requires functionalization of an unactivated carbon atom. This work illustrates the potential of using chemically guided approaches for enzyme discovery.