2014.07.20【英译中】SCI 连载之六

小妮丫头 (流火) 路人甲
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发表于:2014-07-20 22:55 [只看楼主] [划词开启]

2014.07.20【英译中】SCI 连载之六


dasR–N-acetylglucosamine system

dasR-N-乙酰葡糖胺系统

DasR is a global regulator of antibiotic biosynthesis, which links nutrient stress to antibiotic production by Streptomyces (van Wezel and McDowall 2011). N-acetylglucosamine (GlcNAc), a major component of the cell walls of fungi, is the second most abundant polysaccharide in nature. A high concentration of GlcNAc, perhaps mimicking its accumulation after autolytic degradation of the vegetative mycelium, may be a major checkpoint for the onset of secondary metabolism (Rigali et al.2008). The response is transmitted to antibiotic pathway-specific activators through the pleiotropic transcriptional repressor DasR, suggesting a new strategy for activating pathways of secondary metabolite biosynthesis. In S. coelicolor, GlcNAc(10 mM) blocks development and antibiotic production under rich growth conditions, but triggers antibiotic production and sporulation under poor nutritional conditions (i.e., minimal medium), suggesting that the effect of GlcNAc depends on the specific culture conditions. GlcNAc also stimulated antibiotic production by other Streptomyces spp., including Streptomyces clavuligerus, Streptomyces collonus, S. griseus, Streptomyces hygroscopicus, and Streptomyces venezuelae(Rigali et al.2008).

DasR 是世界公认的一种抗生素生物合成“调节者”,在链霉菌属当中参与调节养分胁迫与抗生素产量当中。N-乙酰葡糖胺(GlcNAc)是真菌细胞壁的主要组成成分,也是天然存在的第二大多糖。高浓度的GlcNAc会在营养菌丝体自溶后出现,可能是在模拟它的累积。这种高浓度GlcNAc的出现可能是次级代谢开始的关键节点。这种应答通过多向性的转录抑制蛋白DasR传递给抗生素途径特异动力单位。这种途径的发现对次级代谢生物合成的激活方法具有战略性意义。S. coelicolor中,在营养充足的情况下,GlcNAc(约10毫摩)单元开始形成,抗生素开始产生。但是激发抗生素产生、芽孢形成是在弱营养条件下(如基本培养基),推测影响GlcNAc的因素主要是特异性的培养条件。GlcNAc也受链霉菌属产生的抗生素产量影响,这其中包括Streptomyces clavuligerus, Streptomyces collonus, S. griseus, Streptomyces hygroscopicus, Streptomyces venezuelae

 

The GlcNAc regulon is controlled by the GntR regulator DasR, the DNA-binding activity of which is inhibited by glucosamine-6-phosphate. Introduction of mutations into dasR effectively enhanced antibiotic productivity. For example, the S.coelicolor dasR mutant BAP29 showed three- to fourfold enhanced and accelerated production of pigmented antibiotics (Rigali et al.2008). The position of the DasR binding site in the act II-ORF4 promoter indicates that DasR represses transcription of this gene. Interestingly, the dasR mutant BAP29 was found to be awakened for cryptic gene clusters encoding a hypothetical antibiotic made by a type I modular polyketide synthase (SCO6273-6288), showing that this method is applicable for activating silent gene clusters (Rigali et al.2008).

GlcNAc调控子受GntR的调控者DasR控制,它与DNA的结合活性受葡糖胺-6-磷酸盐抑制。导入dasR基因的突变子能够显著增强抗生素产量。例如,S.coelicolordasR BAP29突变子显示其带色抗生素的产量增强并且加速产生了34倍。在act II-ORF4的启动子中有DasR的结合位点,这表明DasR能够抑制这个基因的转录。有趣的是,dasR基因的BAP29突变株能够有效激活编码由I型聚合酮酶合成的潜在抗生素的潜在基因簇,这表明这种方法对激活沉默基因簇是行之有效的。

分类: 英语

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