Site-Specific Modification of the Anticancer and Antituberculosis Polyether Salinomycin by Biosynthetic Engineering

Autor(es)

Luhavaya, Hanna ^[1] ; Williams, Simon R. ^[2] ; Hong, Hui ^[1] ; de Oliveira, Luciana Gonzaga ^[3] ; Leadlay, Peter F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA - England

^[2] Univ Cambridge, Univ Chem Lab, Cambridge CB2 1EW - England

^[3] Univ Campinas UNICAMP, Dept Organ Chem, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CHEMBIOCHEM; v. 15, n. 14, p. 2081-2085, SEP 22 2014.
• Citações Web of Science: 7

Resumo

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. (AU)

• Processo FAPESP: 11/17510-6 - Estudos sobre a biossíntese e biossíntese combinatória do poliéter ionóforo salinomicina
• Beneficiário: Luciana Gonzaga de Oliveira
• Modalidade de apoio: Bolsas no Exterior - Novas Fronteiras