Identification of the cognate response regulator of the orphan histidine kinase OhkA involved in both secondary metabolism and morphological differentiation in Streptomyces coelicolor
Identification of the cognate response regulator of the orphan histidine kinase OhkA involved in both secondary metabolism and morphological differentiation in Streptomyces coelicolor
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孤儿组氨酸激酶 OhkA 的同源反应调节剂的鉴定，参与天蓝色链霉菌的次生代谢和形态分化
DOI：
10.1007/s00253-021-11442-4
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发表时间：
2021-07
影响因子：
5
通讯作者：
Weihong Jiang
中科院分区：
文献类型：
--
作者：
Guosong Zheng;Panpan Liu;Wenyan He;Hengnuo Tao;Zhen Yang;Chuanwen Sun;Wenfang Wang;Yinhua Lu;Weihong Jiang
摘要 在模型放线菌天蓝色链霉菌中，一种名为OhkA（编码为SCO1596）的孤儿组氨酸激酶（HK）属于细菌双组分调节系统（TCS），已被鉴定参与抗生素生物合成和形态发育的调节。然而，由于其在基因组上的孤立遗传位置，其同源反应调节器（RR）仍然未知，这阻碍了阐明 OhkA 介导的调节机制。在这里，我们根据突变表型变化、转录组学分析和细菌双杂交实验，将孤儿RR OrrA（由SCO3008编码）鉴定为OhkA的同源RR。考虑到孤儿 HK 的伴侣 RR 也是孤儿，因此生成了一个突变体文库，其中这些功能未知的孤儿 RR 编码基因具有框内个体删除。通过表型分析，发现ΔorrAmutant表现出与ΔohkAmutant相似的表型变化，显示放线菌素（ACT）和十一烷基灵菌红素（RED）产量增加，菌落表面呈粉红色。进一步的转录组学分析表明，这两个突变体表现出高度相似的转录组学特征。最后，细菌双杂交系统揭示了OhkA和OrrA之间的直接相互作用。 OhkA 伴侣 RR 的鉴定为深入阐明 OhkA 介导的链霉菌发育和抗生素生物合成调控的分子机制奠定了良好的基础。 要点• OrrA 被鉴定为孤儿组氨酸激酶 OhkA 的伴侣 RR。• ΔorrA 和 ΔohkA 突变体表现出相似的表型和转录组谱。• 揭示了 OrrA 和 OhkA 的特异性相互作用。通过细菌双杂交系统。
AbstractIn the model actinomycete strain,Streptomyces coelicolor, an orphan histidine kinase (HK) named OhkA (encoded bySCO1596), which belongs to bacterial two-component regulatory systems (TCSs), has been identified as being involved in the regulation of both antibiotic biosynthesis and morphological development. However, its cognate response regulator (RR) remains unknown due to its isolated genetic location on the genome, which impedes the elucidation of the mechanism underlying OhkA-mediated regulation. Here, we identified the orphan RR OrrA (encoded bySCO3008) as the cognate RR of OhkA according to mutant phenotypic changes, transcriptomics analysis, and bacterial two-hybrid experiment. Considering that the partner RR of the orphan HK is also orphan, a library of mutants with in-frame individual deletion of these functionally unknown orphan RR-encoding genes were generated. Through phenotypic analysis, it was found that the ∆orrAmutant exhibited similar phenotypic changes as that of the ∆ohkAmutant, showing increased production of actinorhodin (ACT) and undecylprodigiosin (RED), and pink colony surface. Further transcriptomics analysis showed these two mutants exhibited highly similar transcriptomics profiles. Finally, the direct interaction between OhkA and OrrA was revealed by bacterial two-hybrid system. The identification of the partner RR of OhkA lays a good foundation for an in-depth elucidation of the molecular mechanism underlying OhkA-mediated regulation of development and antibiotic biosynthesis inStreptomyces.Key points• OrrA was identified as the partner RR of the orphan histidine kinase OhkA.• The ∆orrA and ∆ohkA mutants showed similar phenotype and transcriptomic profiling.• Specific interaction of OrrA and OhkA was revealed by bacterial two-hybrid system.
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DOI：
10.1099/mic.0.000524
发表时间：
2017-10
期刊：
Microbiology (Reading, England)
影响因子：
--
作者：
Som NF;Heine D;Holmes N;Knowles F;Chandra G;Seipke RF;Hoskisson PA;Wilkinson B;Hutchings MI
通讯作者：
Hutchings MI
影响因子：
3.1
作者：
J. Kormanec;B. Ševčíková
通讯作者：
J. Kormanec;B. Ševčíková
影响因子：
3.6
作者：
Traag, BA;Kelemen, GH;van Wezel, GP
通讯作者：
van Wezel, GP
DOI：
--
发表时间：
2000
期刊：
--
影响因子：
--
作者：
T. Kieser
通讯作者：
T. Kieser
影响因子：
3.2
作者：
Bibb, MJ;Molle, V;Buttner, MJ
通讯作者：
Buttner, MJ