Formation of the Δ18,19 Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme†
نویسندگان
چکیده
Salinomycin is a widely used polyether coccidiostat and was recently found to have antitumor activities. However, the mechanism of its biosynthesis remained largely speculative until now. Reported herein is the identification of an unprecedented function of SlnM, homologous to O-methyltransferases, by correlating its activity with the formation of the Δ(18,19) double bond and bis(spiroacetal). Detailed in vivo and in vitro investigations revealed that SlnM, using positively charged S-adenosylmethionine (SAM) or sinefungin as the cofactor, catalyzed the spirocyclization-coupled dehydration of C19 in a highly atypical fashion to yield salinomycin.
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