It is now well recognized that natural products have directly or indirectly contributed to the discovery and development of as much as 75% of our current treatments for cancer and infectious disease as well as other indications. It cannot be overemphasized that new sources of chemical diversity are essential to the discovery of the next generation of chemotherapeutic agents. Characterization of the polyketide gene clusters responsible for the production of the spirangienes A and B provided detailed information regarding the biochemistry of myxobacterial secondary metabolism as well as significant insights into the evolution of post-PKS enzymes. The implications of these findings, coupled with additional examples, suggest that putative PKS products represent a new source of chemical diversity with chemotherapeutic potential and are thus worthy of further investigation.