Salinomycin (pictured), a natural product from the bacterium Streptomyces albus, is a polyether ionophore antibiotic with potent and selective activity against cancer stem cells. Peter Leadlay and colleagues, University of Cambridge, UK, have cloned and analysed the biosynthetic gene cluster of S. albus in an attempt to better understand the assembly line of salinomycin biosynthesis.
Upon deleting a specific gene—effectively stopping production—they isolate an intermediate that lacks the cis-double bond, showing that oxidative cyclisation occurs after the polyketide is assembled. This work reveals the timing of key stages of the biosynthesis and sets the stage for producing further potent salinomycin analogues by pathway engineering.
- A Late-stage Intermediate in Salinomycin Biosynthesis Revealed by Specific Mutation in the Biosynthetic Gene Cluster
M. Yurkovich, P. Tyrakis, H. Hong, Y. Sun, M. Samborskyy, K. Kamiya, P. Leadlay,