...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Antibiotics: An International Journal >An alternative menaquinone biosynthetic pathway operating in microorganisms: an attractive target for drug discovery to pathogenic Helicobacter and Chlamydia strains.
【24h】

An alternative menaquinone biosynthetic pathway operating in microorganisms: an attractive target for drug discovery to pathogenic Helicobacter and Chlamydia strains.

机译：在微生物中起作用的替代性甲萘醌生物合成途径：是病原性幽门螺杆菌和衣原体菌株发现药物的有吸引力的靶标。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Menaquinone is an essential vitamin as an obligatory component of the electron transfer pathway in microorganisms. Menaquinone has been shown to be derived from chorismate by eight enzymes, designated MenA to -H in Escherichia coli. However, bioinformatic analyses of whole-genome sequences have suggested that some microorganisms, such as Helicobacter pylori and Campylobacter jejuni, which are known to cause gastric carcinoma and diarrhea, respectively, do not have orthologs of most of the men genes, although they synthesize menaquinone. The (13)C-labeling pattern of menaquinone purified from Streptomyces coelicolor A3(2) grown on [U-(13)C]glucose was quite different from that of E. coli, suggesting that an alternative pathway was operating in the strain. We searched for candidate genes participating in the alternative pathway by in silico screening, and the involvement of these genes in the pathway was confirmed by gene-disruption experiments. We also used mutagenesis to isolate mutants that required menaquinone for their growth and used these mutants as hosts for shotgun cloning experiments. Metabolites that accumulated in the culture broth of mutants were isolated and their structures were determined. Taking these results together, we deduced the outline of the alternative pathway, which branched at chorismate in a similar manner to the known pathway but then followed a completely different pathway. As humans and some useful intestinal bacteria, such as lactobacilli, lack the alternative pathway, it would be an attractive target for the development of chemotherapeutics.
机译：甲萘醌是一种必需的维生素，是微生物电子传递途径的必不可少的成分。甲萘醌已被证明是由八种酶的分支酸盐衍生而来，在大肠杆菌中命名为MenA到-H。然而，对全基因组序列的生物信息学分析表明，某些微生物，例如幽门螺杆菌和空肠弯曲菌，分别导致胃癌和腹泻，尽管它们合成了甲萘醌，但它们与大多数男性基因没有直系同源基因。 。从在[U-（13）C]葡萄糖上生长的链霉菌A3（2）纯化的甲萘醌的（13）C标记模式与大肠杆菌完全不同，表明该菌株中存在一条替代途径。我们通过计算机筛选搜索了参与替代途径的候选基因，并且通过基因破坏实验证实了这些基因在途径中的参与。我们还使用诱变方法分离了需要甲萘醌生长的突变体，并将这些突变体用作shot弹枪克隆实验的宿主。分离出突变体培养液中积累的代谢物，并确定其结构。综合这些结果，我们推导出了替代途径的概述，该途径在分支分支上以与已知途径相似的方式分支，然后遵循完全不同的途径。由于人类和某些有用的肠道细菌（如乳酸菌）缺乏替代途径，因此它将成为化学疗法发展的诱人靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号