Production of novel lipopeptide antibiotics related to A54145 by Streptomyces fradiae mutants blocked in biosynthesis of modified amino acids and assignment of lptJ, lptK and lptL gene functions
Production of novel lipopeptide antibiotics related to A54145 by Streptomyces fradiae mutants blocked in biosynthesis of modified amino acids and assignment of lptJ, lptK and lptL gene functions
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DOI：
10.1038/ja.2010.138
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Baltz, Richard H.
中科院分区：
文献类型：
--
作者：
Alexander, Dylan C.;Rock, Jessica;Baltz, Richard H.
A54145 是由弗拉迪链霉菌 (Streptomyces fradiae) 产生的脂肽抗生素复合物。 A54145因子在结构上与达托霉素相关，具有四种修饰氨基酸，达托霉素中仅存在其中一种。我们生成了三个 lptJ、lptK 或 lptL 缺陷突变体，其基因产物参与羟基-Asn(3) (hAsn(3)) 和甲氧基-Asp(9) (moAsp(9)) 的形成。每个突变体都产生与 A54145 相关的新型脂肽，并且这些谱图允许为这些基因分配功能。我们构建了携带这些基因的不同组合以及参与 3-甲基-Glu(12) (3mGlu(12)) 生物合成的 lptl 基因突变的菌株，并且所有重组体都产生了新型脂肽。其中一种化合物在牛表面活性剂存在下表现出非常好的抗菌活性，牛表面活性剂与达托霉素或A54145E相互作用抑制其抗菌活性。抗生素杂志 (2011) 64, 79-87; doi：10.1038/ja.2010.138； 2010 年 11 月 24 日在线发布
A54145 is a complex of lipopeptide antibiotics produced by Streptomyces fradiae. A54145 factors are structurally related to daptomycin, with four modified amino acids, only one of which is present in daptomycin. We generated three mutants defective in lptJ, lptK or lptL, whose gene products are involved in the formation of hydroxy-Asn(3) (hAsn(3)) and methoxy-Asp(9) (moAsp(9)). Each of the mutants produced novel lipopeptides related to A54145 and the profiles allowed assignment of functions for those genes. We constructed strains carrying different combinations of these genes coupled with a mutation in the lptl gene involved in the biosynthesis of 3-methyl-Glu(12) (3mGlu(12)), and all recombinants produced novel lipopeptides. One of the compounds displayed very good antibacterial activity in the presence of bovine surfactant, which interacts with daptomycin or A54145E to inhibit their antibacterial activities. The Journal of Antibiotics (2011) 64, 79-87; doi:10.1038/ja.2010.138; published online 24 November 2010