2014.07.20【英译中】SCI 连载之五

小妮丫头 (流火) 路人甲
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发表于:2014-07-20 00:11 [只看楼主] [划词开启]

2014.07.20【英译中】SCI 连载之五



The recent observation, that several actinomycetes possess two rpoB genes (Vigliotta et al.2005), has suggested a new strategy of activating silent gene expression in bacteria. Two rpoB paralogs, rpoB(S) and rpoB(R), provide Nonomuraea sp. strain 39727 with two functionally distinct and developmentally regulated RNAPs. The product of rpoB(R), the expression of which increases after transition to stationary phase, is characterized by five amino acid substitutions (H426N, S431N, F445M, S474Y, and M581D) located within or close to the rifampicin resistance cluster. The expression of rpoB(R) was found to markedly activate antibiotic biosynthesis, with the rpoB(R)-specific H426N mutation found essential in activating secondary metabolism (Tala et al.2009). Additional rif cluster-associated rpoB(R)-specific missense mutations likely interact functionally with the H426N mutation, leading to the marked effect of rpoB(R). Mutant type, or duplicated, rpoB often exists in nature, with rpoB gene polymorphisms detected in five of 75 inherently rifampicin-resistant actinomycetes isolated from nature, although these polymorphisms were preferentially distributed in the so-called rare actinomycetes, not in Streptomyces spp. Notably, all but one of these rifampicin-resistant rare actinomycete isolates obtained to date were able to produce antibiotics (Tala et al.2009).

近年来观察表明,一部分放线菌有两个rpoB基因。这对在细菌中激活沉默基因的表达具有新的战略意义。两个旁系同源基因rpoB——rpoB(S)rpoB(R),为Nonomuraea sp. 39727菌株提供了两种功能独特并且能发育调节的RNAPrpoB(R)的基因产物在稳定期表达量增加,并且这些产物在利福平抗性区域里或者附近具有5个氨基酸取代基团(H426N, S431N, F445M, S474Y, and M581D)。研究发现rpoB(R)的表达具有显著的激活抗生素生物合成的作用,例如rpoB(R)特异性突变株H426N在激活次级代谢中具有重要作用。除此之外,rif基因簇联合rpoB(R)的特异性错义突变或许能够与H426N突变株有交互作用,能够明显作用于rpoB(R)基因。突变型或者重复的rpoB基因常在自然情况下出现。已经从75中自然存在的具有利福平抗性的放线菌中检测到5个具有多态性的rpoB基因,虽然这些多态性最早是在所说的罕见放线菌中分离得到,而不是在链霉菌属当中。值得注意的是,迄今为止所有利福平抗性西游放线菌隔离群当中只有一个能够产生抗生素。

 

From a practical viewpoint, these findings suggest the intriguing possibility of using rpoB(R)-based technology to improve strains and to search for novel bioactive molecules by activating silent genes. This technology should have greater potential than the simple rif selection currently used to improve the production of secondary metabolites, as the introduction of rpoB(R) enhanced antibiotic production eightfold when compared with the introduction of the H426Y mutation (Tala et al. 2009). It is also of interest to examine whether various rpoB(R) forms found in nature are more capable of activating silent bacterial genes than Nonomuraea rpoB(R). Thus, understanding the status of natural rpoB(R) and utilizing it for cryptic gene activation may provide new horizons for medical and industrial microbiology.

实际上看来,这些发现对利用基于rpoB(R)基因上的技术来激活菌株沉默基因,用以寻找新型活性分子。这项技术在提高次级代谢产物方面,应该比目前简单的rif筛选方法具有更高的潜在利用价值。因为植入rpoB(R)基因相对于导入的H426Y突变型其抗生素产量增加了8倍之多。检测自然环境中发现的多种rpoB(R)基因形式,在激活细菌中的沉默基因方面是否比Nonomuraea中的rpoB(R)基因更有能力。因此,了解自然中的rpoB(R)基因地位并且在激活隐藏基因的利用上能够对医药和工业微生物学方向提供新的视野。


最后编辑于:2014-07-20 00:12
分类: 英语

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