Multidrug Sensitive Yeast Strains, Useful Tools for Chemical Genetics

Multidrug Sensitive Yeast Strains, Useful Tools for Chemical Genetics
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DOI:
10.5772/intechopen.70664
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发表时间:
2017-12
期刊:
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影响因子:
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通讯作者:
Takumi Chinen;K. Hamada;A. Taguchi;Yukihiro Asami;K. Shiomi;Y. Hayashi;T. Usui
Takumi Chinen;K. Hamada;A. Taguchi;Yukihiro Asami;K. Shiomi;Y. Hayashi;T. Usui
中科院分区:
其他
文献类型:
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作者:
Takumi Chinen;K. Hamada;A. Taguchi;Yukihiro Asami;K. Shiomi;Y. Hayashi;T. Usui

文献摘要

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芽生酵母是一种非常有用的真核生物模式生物,在药物筛选、药物评价、靶标鉴定等化学生物学研究中具有重要的应用价值。然而,为了利用酵母进行化学生物学研究,构建适合各种化合物的酵母菌株是必要的,因为它们具有很高的抗药性。因此,除对存活率和遗传实验/操作重要的基因外,所有多药耐药基因的缺失可以在不影响转化、交配或产孢率的情况下增加药物敏感性。导致酿酒酵母多药耐药的主要因素有两个:一个是药物外排系统,另一个是通透性屏障。因此,我们构建了一株对多种药物表现出高度敏感性的菌株,通过使用ATP结合盒转运蛋白来扰乱药物外排系统,并通过引入ERG6诱导系统来抑制膜屏障系统。本文综述了我们的多重药物敏感酵母菌株的构建及其在化学生物学中的应用。
The budding yeast Saccharomyces cerevisiae is a useful eukaryote model organism for application to chemical biology studies, for example, drug screening, drug evaluation, and target identification. To use yeast for chemical biology research, however, it has been necessary to construct yeast strains suitable for various compounds because of their high drug resistance. Hence, the deletion of all multidrug resistance genes except for those that are important for viability and for genetic experiments/manipulation could increase the drug sensitivity without influencing the transformation, mating, or sporulation effi -ciency. There are two major factors conferring multidrug resistance in S. cerevisiae : one is the drug efflux system and the other is the permeability barrier. We therefore constructed a strain which shows high sensitivity to multiple drugs by disrupting the drug efflux system using ATP-binding cassette transporters and suppressing the membrane barrier system by introducing an ERG6-inducible system. In this review, we discuss the construc tion of our multidrug-sensitive yeast strains and their application in chemical biology.