Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms.
J Am Chem Soc. 2017 05 31;139(21):7188-7191
Authors: Solinski AE, Koval AB, Brzozowski RS, Morrison KR, Fraboni AJ, Carson CE, Eshraghi AR, Zhou G, Quivey RG, Voelz VA, Buttaro BA, Wuest WM
The oral microbiome is a dynamic environment inhabited by both commensals and pathogens. Among these is Streptococcus mutans, the causative agent of dental caries, the most prevalent childhood disease. Carolacton has remarkably specific activity against S. mutans, causing acid-mediated cell death during biofilm formation; however, its complex structure limits its utility. Herein, we report the diverted total synthesis and biological evaluation of a rationally designed library of simplified analogs that unveiled three unique biofilm phenotypes further validating the role of natural product synthesis in the discovery of new biological phenomena.
PMID: 28502178 [PubMed – indexed for MEDLINE]