Characterization of the mupirocin biosynthesis gene cluster from Pseudomonas fluorescens NCIMB 10586
Characterization of the mupirocin biosynthesis gene cluster from Pseudomonas fluorescens NCIMB 10586
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DOI：
10.1016/s1074-5521(03)00091-7
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发表时间：
2003-05-01
影响因子：
--
通讯作者：
Thomas, CM
中科院分区：
文献类型：
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作者：
El-Sayed, AK;Hothersall, J;Thomas, CM
由荧光假单胞菌NCIMB 10586产生的聚酮抗生素莫匹罗星（假单胞菌酸）竞争性抑制细菌异亮氨酰-tRNA合酶，并可用于控制金黄色葡萄球菌，特别是耐甲氧西林金黄色葡萄球菌。已对74 kb莫匹罗星生物合成簇进行了测序，并鉴定了许多开放阅读框（ORF）的推定酶功能。莫匹罗星簇是六个较大ORF（mmPA-F）的组合，其含有类似于聚酮合酶和脂肪酸合酶I型系统的多功能蛋白质的几个结构域，以及单个基因（mupA-X和macpA-E），其中一些显示出与II型系统（mupB、mupD、mupG和mupS）的相似性。基因敲除实验证明了区域在莫匹罗星生产中的重要性，并且被破坏的基因的互补证实了表型不是由于极性效应。基于序列和生化证据，提出了莫匹罗星生物合成的模型。
The polyketide antibiotic mupirocin (pseudomonic acid) produced by Pseudomonas fluorescens NCIMB 10586 competitively inhibits bacterial isoleucyl-tRNA synthase and is useful in controlling Staphylococcus aureus, particularly methicillin-resistant Staphylococcus aureus. The 74 kb mupirocin biosynthesis cluster has been sequenced, and putative enzymatic functions of many of the open reading frames (ORFs) have been identified. The mupirocin cluster is a combination of six larger ORFs (mmpA-F), containing several domains resembling the multifunctional proteins of polyketide synthase and fatty acid synthase type I systems, and individual genes (mupA-X and macpA-E), some of which show similarity to type II systems (mupB, mupD, mupG, and mupS). Gene knockout experiments demonstrated the importance of regions in mupirocin production, and complementation of the disrupted gene confirmed that the phenotypes were not due to polar effects. A model for mupirocin biosynthesis is presented based on the sequence and biochemical evidence.