Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme

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,...

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Autores principales: Jiang, Chunyan, Qi, Zhen, Kang, Qianjin, Liu, Jing, Jiang, Ming, Bai, Linquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY‐VCH Verlag 2015
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744726/
https://www.ncbi.nlm.nih.gov/pubmed/26096919
http://dx.doi.org/10.1002/anie.201503561
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author Jiang, Chunyan
Qi, Zhen
Kang, Qianjin
Liu, Jing
Jiang, Ming
Bai, Linquan
author_facet Jiang, Chunyan
Qi, Zhen
Kang, Qianjin
Liu, Jing
Jiang, Ming
Bai, Linquan
author_sort Jiang, Chunyan
collection PubMed
description 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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spelling pubmed-47447262016-02-18 Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme Jiang, Chunyan Qi, Zhen Kang, Qianjin Liu, Jing Jiang, Ming Bai, Linquan Angew Chem Int Ed Engl Communications 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. WILEY‐VCH Verlag 2015-06-11 2015-07-27 /pmc/articles/PMC4744726/ /pubmed/26096919 http://dx.doi.org/10.1002/anie.201503561 Text en © 2015 The Authors. Published by Wiley‐VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non‐Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Open access.
spellingShingle Communications
Jiang, Chunyan
Qi, Zhen
Kang, Qianjin
Liu, Jing
Jiang, Ming
Bai, Linquan
Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme
title Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme
title_full Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme
title_fullStr Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme
title_full_unstemmed Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme
title_short Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase‐like Enzyme
title_sort formation of the δ(18,19) double bond and bis(spiroacetal) in salinomycin is atypically catalyzed by slnm, a methyltransferase‐like enzyme
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744726/
https://www.ncbi.nlm.nih.gov/pubmed/26096919
http://dx.doi.org/10.1002/anie.201503561
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