Nature Chemical Biology ( IF 12.9 ) Pub Date : 2016-03-14 , DOI: 10.1038/nchembio.2043 Janne J Koskimäki , Marena Kajula , Juho Hokkanen , Emmi-Leena Ihantola , Jong H Kim , Heidi Hautajärvi , Elina Hankala , Marko Suokas , Johanna Pohjanen , Olga Podolich , Natalia Kozyrovska , Ari Turpeinen , Mirva Pääkkönen , Sampo Mattila , Bruce C Campbell , Anna Maria Pirttilä
Bacteria rely mainly on enzymes, glutathione and other low–molecular weight thiols to overcome oxidative stress. However, hydroxyl radicals are the most cytotoxic reactive oxygen species, and no known enzymatic system exists for their detoxification. We now show that methyl-esterified dimers and trimers of 3-hydroxybutyrate (ME-3HB), produced by bacteria capable of polyhydroxybutyrate biosynthesis, have 3-fold greater hydroxyl radical–scavenging activity than glutathione and 11-fold higher activity than vitamin C or the monomer 3-hydroxybutyric acid. We found that ME-3HB oligomers protect hypersensitive yeast deletion mutants lacking oxidative stress–response genes from hydroxyl radical stress. Our results show that phaC and phaZ, encoding polymerase and depolymerase, respectively, are activated and polyhydroxybutyrate reserves are degraded for production of ME-3HB oligomers in bacteria infecting plant cells and exposed to hydroxyl radical stress. We found that ME-3HB oligomer production is widespread, especially in bacteria adapted to stressful environments. We discuss how ME-3HB oligomers could provide opportunities for numerous applications in human health.
中文翻译:
甲基酯化的3-羟基丁酸酯低聚物可保护细菌免受羟基自由基的侵害
细菌主要依靠酶,谷胱甘肽和其他低分子量硫醇来克服氧化应激。然而,羟基自由基是最具细胞毒性的活性氧种类,并且不存在用于其解毒的已知酶促系统。我们现在显示,能够合成多羟基丁酸酯的细菌产生的3-羟基丁酸酯(ME-3HB)甲基酯化的二聚体和三聚体具有比谷胱甘肽高3倍的清除羟自由基活性和比维生素C或11倍高的11倍活性。单体3-羟基丁酸。我们发现,ME-3HB低聚物可保护缺乏氧化应激反应基因的超敏酵母缺失突变体免受羟自由基应激的影响。我们的结果表明phaC和phaZ分别编码聚合酶和解聚酶的β-内切酶被激活,并且聚羟基丁酸酯储备被降解,以在感染植物细胞并暴露于羟基自由基胁迫的细菌中产生ME-3HB寡聚体。我们发现ME-3HB低聚物的产生非常普遍,尤其是在适应压力环境的细菌中。我们讨论了ME-3HB低聚物如何为人体健康中的众多应用提供机会。