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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reverse biological engineering of hrdB to enhance the production of avermectins in an industrial strain of Streptomyces avermitilis
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Reverse biological engineering of hrdB to enhance the production of avermectins in an industrial strain of Streptomyces avermitilis

机译：hrdB的逆向生物学工程可提高阿维链霉菌工业菌株中阿维菌素的产量

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摘要

Avermectin and its analogues are produced by the actinomycete Streptomyces avermitilis and are widely used in the field of animal health, agriculture, and human health. Here we have adopted a practical approach to successfully improve avermectin production in an industrial overproducer. Transcriptional levels of the wild-type strain and industrial overproducer in production cultures were monitored using microarray analysis. The avermectin biosynthetic genes, especially the pathway-specific regulatory gene, aveR, were up-regulated in the high-producing strain. The upstream promoter region of aveR was predicted and proved to be directly recognized by σ~(hrdB) in vitro. A mutant library of hrdB gene was constructed by error-prone PCR and selected by high-throughput screening. As a result of evolved hrdB expressed in the modified avermectin high-producing strain, 6.38 g/L of avermectin B1a was produced with over 50% yield improvement, in which the transcription level of aveR was significantly increased. The relevant residues were identified to center in the conserved regions. Engineering of the hrdB gene can not only elicit the overexpression of aveR but also allows for simultaneous transcription of many other genes. The results indicate that manipulating the key genes revealed by reverse engineering can effectively improve the yield of the target metabolites, providing a route to optimize production in these complex regulatory systems.
机译：阿维菌素及其类似物由放线菌阿维链霉菌产生，并广泛用于动物健康，农业和人类健康领域。在这里，我们采用了一种实用的方法来成功提高工业生产商中阿维菌素的生产。使用微阵列分析监测生产培养物中野生型菌株和工业过量生产者的转录水平。在高产菌株中，阿维菌素的生物合成基因，特别是途径特异性调控基因，aveR，被上调。预测了aveR的上游启动子区域，并在体外被σ〜（hrdB）直接识别。通过易错PCR构建hrdB基因突变文库，并通过高通量筛选进行选择。作为在改良的阿维菌素高产菌株中表达的hrdB进化结果，产生了6.38 g / L的阿维菌素B1a，产量提高了50％以上，其中aveR的转录水平显着提高。确定了相关的残基位于保守区的中心。 hrdB基因的工程设计不仅可以引起aveR的过表达，还可以同时转录许多其他基因。结果表明，通过逆向工程揭示的关键基因可以有效提高目标代谢物的产量，为优化这些复杂调控系统的生产提供了一条途径。

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  • 作者

    Ying Zhuo; Wenquan Zhang; Difei Chen; Hong Gao; Jun Tao; Mei Liu; Zhongxuan Gou; Xianlong Zhou; Bang-Ce Ye; Qing Zhang; Siliang Zhang; Li-Xin Zhang;

  • 作者单位

    Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China Graduate University of Chinese Academy of Sciences, Beijing 100190, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China Graduate University of Chinese Academy of Sciences, Beijing 100190, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China;

    rnState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;

    rnHebei Veyong Bio-Chemical Co., Ltd., Shijiazhuang, Hebei 050031, China;

    rnState Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;

    rnChinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    precision engineering; RNA polymerase; overproduction;

    机译：精密工程;RNA聚合酶;生产过剩;

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