title: Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase-like Enzyme.
abstract: 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.
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd. Shanghai 200240 (China).
authors.forename: Chunyan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd. Shanghai 200240 (China).
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd. Shanghai 200240 (China).
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Kang
authors.affiliation: Institute of Health Sciences, School of Chemistry and Chemical Engineering, Anhui University, Hefei 230601 (China).
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd. Shanghai 200240 (China).
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Rd. Shanghai 200240 (China). bailq@sjtu.edu.cn.
authors.forename: Linquan
authors.initials: L
authors.lastname: Bai
mesh_terms: D002384:Catalysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008780:Methyltransferases / Q000737:chemistry*; D008958:Models, Molecular; D061065:Polyketides / Q000737:chemistry*; D011714:Pyrans / Q000737:chemistry*; D000095662:Polyether Polyketides
chemical_list: D008780:Methyltransferases; D061065:Polyketides; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: NMR spectroscopy; biosynthesis; computational chemistry; enzyme catalysis; polyketides