Discovery of the Antibiotic Phosacetamycin via a New Mass Spectrometry-Based Method for Phosphonic Acid Detection

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• 作者：Bradley S. Evans ; Changming Zhao ; Jiangtao Gao ; Courtney M. Evans ; Kou-San Ju ; James R. Doroghazi ; Wilfred A. van der Donk ; Neil L. Kelleher ; William W. Metcalf
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：May 17, 2013
• 年：2013
• 卷：8
• 期：5
• 页码：908-913
• 全文大小：385K
• 年卷期：v.8,no.5(May 17, 2013)
• ISSN：1554-8937

文摘

Naturally occurring phosphonates such as phosphinothricin (Glufosinate, a commercially used herbicide) and fosfomycin (Monurol, a clinically used antibiotic) have proved to be potent and useful biocides. Yet this class of natural products is still an under explored family of secondary metabolites. Discovery of the biosynthetic pathways responsible for the production of these compounds has been simplified by using gene based screening approaches, but detection and identification of the natural products the genes produce have been hampered by a lack of high-throughput methods for screening potential producers under various culture conditions. Here, we present an efficient mass-spectrometric method for the selective detection of natural products containing phosphonate and phosphinate functional groups. We have used this method to identify a new phosphonate metabolite, phosacetamycin, whose structure, biological activity, and biosynthetic gene cluster are reported.