Institute of Gene Biology of the Russian Academy of Sciences, Moscow, Russia.
J Bacteriol. 2013 Sep;195(18):4129-37. doi: 10.1128/JB.00665-13. Epub 2013 Jul 12.
Escherichia coli microcin B (Ec-McB) is a posttranslationally modified antibacterial peptide containing multiple oxazole and thiazole heterocycles and targeting the DNA gyrase. We have found operons homologous to the Ec-McB biosynthesis-immunity operon mcb in recently sequenced genomes of several pathovars of the plant pathogen Pseudomonas syringae, and we produced two variants of P. syringae microcin B (Ps-McB) in E. coli by heterologous expression. Like Ec-McB, both versions of Ps-McB target the DNA gyrase, but unlike Ec-McB, they are active against various species of the Pseudomonas genus, including human pathogen P. aeruginosa. Through analysis of Ec-McB/Ps-McB chimeras, we demonstrate that three centrally located unmodified amino acids of Ps-McB are sufficient to determine activity against Pseudomonas, likely by allowing specific recognition by a transport system that remains to be identified. The results open the way for construction of McB-based antibacterial molecules with extended spectra of biological activity.
大肠杆菌微菌素 B（Ec-McB）是一种经翻译后修饰的抗菌肽，含有多个噁唑和噻唑杂环，靶向 DNA 回旋酶。我们在最近测序的几种植物病原体丁香假单胞菌的基因组中发现了与 Ec-McB 生物合成-免疫操纵子 mcb 同源的操纵子，并且通过异源表达在大肠杆菌中产生了两种变体的丁香假单胞菌微菌素 B（Ps-McB）。与 Ec-McB 一样，两种版本的 Ps-McB 均靶向 DNA 回旋酶，但与 Ec-McB 不同的是，它们对包括人类病原体铜绿假单胞菌在内的各种假单胞菌属物种均具有活性。通过 Ec-McB/Ps-McB 嵌合体的分析，我们证明了 Ps-McB 中三个位于中心的未修饰氨基酸足以决定对假单胞菌的活性，可能是通过允许特定的识别由一个仍然有待鉴定的运输系统。该结果为构建具有扩展生物活性谱的基于 McB 的抗菌分子开辟了道路。
