a natural plasmid uniquely encodes two biosynthetic pathways creating a potent anti-mrsa antibiotic独特的天然质粒编码两个创建强有力的anti-mrsa抗生素生物合成途径.pdfVIP

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a natural plasmid uniquely encodes two biosynthetic pathways creating a potent anti-mrsa antibiotic独特的天然质粒编码两个创建强有力的anti-mrsa抗生素生物合成途径.pdf

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a natural plasmid uniquely encodes two biosynthetic pathways creating a potent anti-mrsa antibiotic独特的天然质粒编码两个创建强有力的anti-mrsa抗生素生物合成途径

A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic 1. 1. 2 2 1 Daisuke Fukuda , Anthony S. Haines , Zhongshu Song , Annabel C. Murphy , Joanne Hothersall , 1 1 2 2 2 Elton R. Stephens , Rachel Gurney , Russell J. Cox , John Crosby , Christine L. Willis , Thomas J. 2 1 Simpson , Christopher M. Thomas * 1 School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, 2 School of Chemistry, University of Bristol, Cantock’s Close, Bristol, United Kingdom Abstract Background: Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin. Methodology/Principal Findings: High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters. Targeted gene knockouts confirmed the role of these clusters in biosynthesis of the two separate components, pseudomonic acid and the pyrrothine, and identified a putative amide synthetase that joins them together. Feeding mupirocin to a mutant unable to make the endogenous pseudomonic acid created a novel hybrid with the pyrrothine via ‘‘mutasynth