斯特列普顿生物合成:一种新的细菌素家族的原型
Wendy L Kelly1, Lisa Pan, Chaoxuan Li
1School of Chemistry and Biochemistry and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA. wendy.kelly@chemistry.gatech.edu
Journal of the American Chemical Society
|March 7, 2009
概括
研究人员确定了 thiostrepton prepeptide (TsrA) 和负责 Streptomyces laurentii 中的 thiopeptide 抗生素生物合成的基因集群. 这项研究阐明了生产这些抗微生物的复杂后翻译性修改.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 硫类抗生素是复杂的,高度修饰的代谢产物,具有特有的宏观环形支架.
- 它们复杂的生物发生,涉及脱水氨基酸和 thiazole 环,已被了解得很少.
- 关键的结构特征包括脱水烯/烯环和潜在的酸/酸替代物.
研究的目的:
- 为了阐明硫类抗生素,特别是硫类抗生素的生物合成途径.
- 鉴定涉及于提欧前体的翻译后修饰的基因和酶.
- 为了建立在更广泛的抗微生物的家族内thiopeptides的分类.
主要方法:
- 全基因组扫描Streptomyces laurentii以确定潜在的生物合成基因.
- 基因突变 (TSrT的破坏) 来确认基因参与生物合成.
- 代谢物分析以检测由基因破坏引起的新型化合物.
- 关键酶的识别和表征,包括氨基转移酶和氨基转移酶.
主要成果:
- 提奥斯特前 (TsrA) 的鉴定及其在生物合成中的关键作用.
- 负责列生产的基因集群 (TSR) 的表征.
- 对tsrT基因的干扰导致了列的损失,并检测出了一种新的代谢物.
- 有证据表明,TSR位点编码了用于将托转化为酸部分的酶.
结论:
- 这项研究成功地确定了斯特生物合成途径的关键组成部分.
- 据证实,硫是细菌素,是通过遗传编码产生的抗菌.
- 对前的广泛的翻译后修改对于成熟的硫类抗生素形成至关重要.
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