Organic Peroxide-Sensing Repressor OhrR Regulates Organic Hydroperoxide Stress Resistance and Avermectin Production in Streptomyces avermitilis.

Organic Peroxide-Sensing Repressor OhrR Regulates Organic Hydroperoxide Stress Resistance and Avermectin Production in Streptomyces avermitilis.
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有机过氧化物传感阻遏物 OhrR 调节阿维链霉菌的有机氢过氧化物应激抵抗和阿维菌素生产

DOI:
10.3389/fmicb.2018.01398
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发表时间:
2018
影响因子:
5.2
通讯作者:
Chen Z
Chen Z
中科院分区:
生物学2区
文献类型:
--
作者:
Sun M;Lyu M;Wen Y;Song Y;Li J;Chen Z

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阿维链霉菌是阿维菌素的工业化生产者,阿维菌素是一种重要的驱虫剂,广泛应用于农业、兽医和人类医学。在阿维菌素发酵过程中,阿维菌素链霉菌暴露在好氧呼吸产生的有机过氧化物中。我们研究了Marr家族转录调控因子OhrR在阿维链霉菌氧化应激反应和阿维菌素生产中的作用。阿维链霉菌基因组编码两种有机抗过氧化氢蛋白:OhrB1和OhrB2。OhrB2是有机过氧化应激反应中的主要抗性蛋白。在没有有机过氧化氢的情况下,OhrR的还原形式通过与启动子区域的OhrR盒结合来抑制ohrB2基因的表达。在有机过氧化物存在下,OhrR的氧化形式从OhrR盒中解离出来,并且ohrB2的表达通过去阻遏而增加。OhrR也作为抑制因子来调节自身的表达。一个ohrR缺失突变体(称为DohrR)显示了阿维菌素产量的增强。我们的研究结果表明,阿维链霉菌中的OhrR通过调节途径特异性调控基因aver的表达来抑制阿维菌素的产生。OhrR还通过负调控pykA2和CTAB/tkt2-tal2-zwf2-opcA2-PGL的表达,在糖酵解和磷酸戊糖(PP)途径中发挥调节作用。
The bacterium Streptomyces avermitilis is an industrial-scale producer of avermectins, which are important anthelmintic agents widely used in agriculture, veterinary medicine, and human medicine. During the avermectin fermentation process, S. avermitilis is exposed to organic peroxides generated by aerobic respiration. We investigated the role of MarR-family transcriptional regulator OhrR in oxidative stress response and avermectin production in S. avermitilis. The S. avermitilis genome encodes two organic hydroperoxide resistance proteins: OhrB1 and OhrB2. OhrB2 is the major resistance protein in organic peroxide stress responses. In the absence of organic peroxide, the reduced form of OhrR represses the expression of ohrB2 gene by binding to the OhrR box in the promoter region. In the presence of organic peroxide, the oxidized form of OhrR dissociates from the OhrR box and the expression of ohrB2 is increased by derepression. OhrR also acts as a repressor to regulate its own expression. An ohrR-deletion mutant (termed DohrR) displayed enhanced avermectin production. Our findings demonstrate that OhrR in S. avermitilis represses avermectin production by regulating the expression of pathway-specific regulatory gene aveR. OhrR also plays a regulatory role in glycolysis and the pentose phosphate (PP) pathway by negatively controlling the expression of pykA2 and ctaB/tkt2-tal2-zwf2-opcA2-pgl.
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