MUTASYNTHESIS OF SIDEROPHORE ANALOGS BY PSEUDOMONAS-AERUGINOSA
MUTASYNTHESIS OF SIDEROPHORE ANALOGS BY PSEUDOMONAS-AERUGINOSA
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DOI：
10.1073/pnas.88.5.1878
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发表时间：
1991-03-01
影响因子：
11.1
通讯作者：
COX, CD
中科院分区：
文献类型：
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作者：
ANKENBAUER, RG;STALEY, AL;COX, CD
革兰氏阴性细菌铜绿假单胞菌产生酚类铁载体绿脓螯铁蛋白。 水杨酸是绿脓菌螯铁蛋白生物合成途径中的中间体，并且在水杨酸生物合成中被阻断的突变体（Sal-）能够将外源提供的水杨酸掺入绿脓菌螯铁蛋白中。 将铜绿假单胞菌Sal-突变体与13种水杨酸类似物一起孵育，发现其中三种（5-氟水杨酸、4-甲基水杨酸和3-羟基吡啶甲酸）掺入绿脓菌螯铁蛋白类似物中，通常称为5-氟绿脓菌螯铁蛋白、4-甲基绿脓菌螯铁蛋白和6-氮杂绿脓菌螯铁蛋白. 突变合成产物的结构通过H-1和C-13 NMR和高分辨率快速原子轰击质谱法证实为与绿脓菌螯铁蛋白相同，除了芳环中的预期变化。 在铁转运测定中测定三种绿脓菌螯铁蛋白类似物的生物活性。 与绿脓菌螯铁蛋白相比，4-甲基绿脓菌螯铁蛋白在测定中更具活性，而5-氟绿脓菌螯铁蛋白和6-氮杂绿脓菌螯铁蛋白的活性显著降低。 在共孵育试验中，5-fluorophyochelin基本上抑制铁转运的绿脓菌螯铁蛋白; 4-甲基绿脓菌螯铁蛋白和6-azapyochelin没有表现出这种抑制作用。
The Gram-negative bacterium Pseudomonas aeruginosa produces the phenolic siderophore pyochelin. Salicylic acid is an intermediate in the pyochelin biosynthetic pathway, and mutants blocked in salicylic acid biosynthesis (Sal-) are able to incorporate exogenously supplied salicylic acid into pyochelin. A P. aeruginosa Sal- mutant was incubated with 13 salicylic acid analogues and was found to incorporate three (5-fluorosalicylic acid, 4-methylsalicylic acid, and 3-hydroxypicolinic acid) into pyochelin analogues, trivially designated as 5-fluoropyochelin, 4-methylpyochelin, and 6-azapyochelin. The structures of the mutasynthetic products were confirmed by H-1 and C-13 NMR and high-resolution fast atom bombardment mass spectrometry as being identical to pyochelin except for the expected changes in the aromatic ring. The biological activity of the three pyochelin analogues was determined in iron transport assays. In comparison to pyochelin, 4-methylpyochelin was more active in the assays whereas the activities of 5-fluoropyochelin and 6-azapyochelin were markedly decreased. In coincubation assays, 5-fluoropyochelin substantially inhibited iron transport by pyochelin; 4-methylpyochelin and 6-azapyochelin did not demonstrate this inhibitory effect.