• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Mechanism Studies on Fungal Type I Highly-Reducing Polyketide Synthases and Polyketide Synthase-Nonribosomal Peptide Synthetase Hybrids.
【24h】

Mechanism Studies on Fungal Type I Highly-Reducing Polyketide Synthases and Polyketide Synthase-Nonribosomal Peptide Synthetase Hybrids.

机译：真菌I型高还原性聚酮化合物合酶和聚酮化合物合酶-非核糖体肽合成酶杂种的机理研究。

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

Filamentous fungi are known as promising sources for bio-active natural products, some of which are blockbuster drugs, such as penicillin and lovastatin. Fungal polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) are large highly complex multidomain megasynthetases with complex programming rules. Different from their well-studied bacterial counterparts, the mechanisms of these megasynthases are not well understood to date. The thesis focuses on mechanism study of two fungal highly reducing PKSs involved in lovastatin biosynthesis and a PKS-NRPS hybrid from Apsergillus sp..;Using the developed expression system in S. cerevisiae, we were able to probe the property of these enzymes under different conditions with in vivo experiment in the heterologous host and in vitro assays.;In the lovastatin project, we observed and studied interaction between highly-reducing polyketide synthase (HR-PKS) and its product releasing partner. These PKS/releasing-enzyme pairs could widely exist in the HR-PKS systems. It also shows applications to drug industry because the efficiency of product releasing from PKSs could directly determine the yield of the natural products. In the study related to PKS-NRPS hybrid, we were able to be the first group to reconstitute full function of this type of megasynthetase in vitro and probe the programming on both PKS and NRPS module in this hybrid. More importantly, we also observed interaction between these two modules.
机译：丝状真菌被认为是具有生物活性的天然产物的有前途的来源，其中一些是重磅炸弹药物，例如青霉素和洛伐他汀。真菌聚酮化合物合成酶（PKS）和非核糖体肽合成酶（NRPS）是具有复杂编程规则的大型高度复杂的多域大型合成酶。与它们经过充分研究的细菌类似物不同，这些巨合酶的机制迄今尚未得到很好的了解。本文着重研究了两种与洛伐他汀生物合成有关的真菌高度还原性PKSs和来自Apsergillus sp。的PKS-NRPS杂种的机理；利用酿酒酵母中发达的表达系统，我们能够探究这些酶在不同条件下的特性。在洛伐他汀项目中，我们观察和研究了高度还原的聚酮化合物合酶（HR-PKS）及其产物释放伴侣之间的相互作用。这些PKS /释放酶对可能广泛存在于HR-PKS系统中。它还显示了在制药行业的应用，因为从PKS释放产品的效率可以直接决定天然产品的产量。在与PKS-NRPS杂种有关的研究中，我们能够成为第一个在体外重构这种类型的合成酶全功能的研究小组，并探讨了该杂种中PKS和NRPS模块的编程。更重要的是，我们还观察了这两个模块之间的相互作用。

著录项

  • 作者

    Xu, Wei.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Engineering Chemical.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 104 p.
  • 总页数 104
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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