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Implication of orphan histidine kinase (OhkAsp) in biosynthesis of doxorubicin and daunorubicin in Streptomyces peucetius ATCC 27952
Microbiological Research ( IF 6.1 ) Pub Date : 2018-05-22 , DOI: 10.1016/j.micres.2018.05.007
Anaya Raj Pokhrel , Hue Thi Nguyen , Dipesh Dhakal , Amit Kumar Chaudhary , Jae Kyung Sohng

The orphan histidine kinase (HK) from Streptomyces peucetius ATCC 27952 (ohkAsp) was found to be implicated in the regulation of doxorubicin (DOX)/daunorubicin (DNR) biosynthesis, self-defense and developmental attributes. OhkAsp is a homolog of OhkA from Streptomyces coelicolor and Streptomyces avermitilis (with 73 and 75% identity). As in its homologs, S. peucetius mutant with deletion of ohkAsp was found to enhance metabolite biosynthesis and impaired the morphological differentiation. But, unlike its homologs from Streptomyces coelicolor and Streptomyces avermitilis, differential enhancement in level of secondary metabolite production was found in overexpression mutants apart from deletion mutant. The deflection in characteristics of OhkA in its homologue from S. peucetius ATCC 27952, and its imminent implications was monitered by making various mutants with differential expression level of ohkAsp. The variations were observed in the morphology of mutants, transcriptional level of effectors and regulators of DOX/DNR biosynthesis pathway, DOX/DNR precursor pool and biomass accumulation. Based on comparisons of domain arrangements among its homologs, Low Complexity Region (LCR) present on the OhkAsp was the only domain that stood out. Further, the LCR on OhkAsp was found to be overlapping with a putative receiver domain responsible for interaction with response regulator. The imminent implications of differential expression level of ohkAsp on: regulation and biosynthesis of DOX/DNR, morphological differentiation, DOX/DNR precursor pool and biomass accumulation were explored in this study.



中文翻译:

孤组氨酸激酶(OhkAsp)在多聚链霉菌ATCC 27952中阿霉素和柔红霉素生物合成中的意义

发现来自Pe Streptomyces peucetius ATCC 27952(ohkAsp)的孤儿组氨酸激酶(HK)与阿霉素(DOX)/柔红霉素(DNR)生物合成,自卫和发育特性的调节有关。OhkAsp是来自天蓝色链霉菌阿维链霉菌的OhkA的同源物(具有73%和75%的同一性)。如同其同源物一样,发现带有ohkAsp缺失的S. peucetius突变体可增强代谢物的生物合成,并损害其形态分化。但是,不同于其来自天蓝色链霉菌阿维链霉菌的同系物除缺失突变体外,在过表达突变体中发现次级代谢产物产生水平的差异性增强。通过制备具有hkksp差异表达水平的各种突变体,可以控制OhkA在其与S. peucetius ATCC 27952同源物中的特性的偏差以及其迫在眉睫的含义。。观察到突变体的形态,DOX / DNR生物合成途径的效应子和调节子的转录水平,DOX / DNR前体库和生物量积累的变化。根据同系物之间域排列的比较,OkAsp上存在的低复杂度区域(LCR)是唯一突出的域。此外,发现在OhkAsp上的LCR与负责与响应调节剂相互作用的推定的受体域重叠。本研究探讨了ohkAsp差异表达水平对DOX / DNR的调控和生物合成,形态分化,DOX / DNR前体库和生物量积累的直接影响。

更新日期:2018-05-22
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