Repository logo

Site-specific modification of the anticancer and antituberculosis polyether salinomycin by biosynthetic engineering.

No Thumbnail Available



Change log


Luhavaya, Hanna 
Williams, Simon R 
Hong, Hui 
Gonzaga de Oliveira, Luciana 
Leadlay, Peter F 


The complex bis-spiroacetal polyether ionophore salinomycin has been identified as a uniquely selective agent against cancer stem cells and is also strikingly effective in an animal model of latent tuberculosis. The basis for these important activities is unknown. We show here that deletion of the salE gene abolishes salinomycin production and yields two new analogues, in both of which the C18C19 cis double bond is replaced by a hydroxy group stereospecifically located at C19, but which differ from each other in the configuration of the bis-spiroacetal. These results identify SalE as a novel dehydratase and demonstrate that biosynthetic engineering can be used to redirect the reaction cascade of oxidative cyclization to yield new salinomycin analogues for use in mechanism-of-action studies.



biosynthesis, dehydratases, ionophores, polyketides, spiroacetals, Acetals, Antineoplastic Agents, Antitubercular Agents, Bacterial Proteins, Biosynthetic Pathways, Cyclization, Humans, Ionophores, Metabolic Engineering, Mutation, Oxidation-Reduction, Pyrans, Spiro Compounds, Streptomyces

Journal Title


Conference Name

Journal ISSN


Volume Title



Biotechnology and Biological Sciences Research Council (BB/I002413/1)
Biotechnology and Biological Sciences Research Council (BB/D018943/1)
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and by Biotica Technology Ltd. through an Industrial Partnership Award BB/I002513/1 to P. F. Leadlay. H. Luhavaya acknowledges a studentship from the Cambridge Overseas Trust and S. R. Williams acknowledges a studentship from the Todd-Raphael Fund and Prof. Ian Paterson. L. Gonzaga de Oliveira was supported by the São Paulo Research Foundation (2011/17510-6). P. F. Leadlay is a Research Awardee of the Alexander von Humboldt Foundation.