Feast or famine:: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces
Feast or famine:: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces
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DOI：
10.1038/embor.2008.83
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发表时间：
2008-07-01
期刊：
影响因子：
7.7
通讯作者：
van Wezel, Gilles P.
中科院分区：
文献类型：
--
作者：
Rigali, Sebastien;Titgemeyer, Fritz;van Wezel, Gilles P.
土壤原核链霉菌属的成员产生许多次级代谢产物，包括抗生素和抗肿瘤剂。它们的形成伴随着由生境的营养状况引发的发育的开始。我们提出了第一个完整的信号级联从营养传感发展和抗生素的生物合成。我们发现，高浓度的N-乙酰葡糖胺-可能模仿N-乙酰葡糖胺的积累后，自溶降解的营养菌丝体-是一个主要的检查点的发病的次生代谢。该反应通过多效性转录抑制子DasR传递给抗生素途径特异性激活剂，DasR的调节子还包括所有N-乙酰葡糖胺相关的分解代谢基因。这些结果使我们能够设计一种新的策略来激活次生代谢物生物合成的途径。这种“神秘”途径在放线菌基因组中非常丰富，从而为对抗多种耐药病原体和癌症提供了新的前景。
Members of the soil-dwelling prokaryotic genus Streptomyces produce many secondary metabolites, including antibiotics and anti-tumour agents. Their formation is coupled with the onset of development, which is triggered by the nutrient status of the habitat. We propose the first complete signalling cascade from nutrient sensing to development and antibiotic biosynthesis. We show that a high concentration of N-acetylglucosamine-perhaps mimicking the accumulation of N-acetylglucosamine after autolytic degradation of the vegetative mycelium-is a major checkpoint for the onset of secondary metabolism. The response is transmitted to antibiotic pathway-specific activators through the pleiotropic transcriptional repressor DasR, the regulon of which also includes all N-acetylglucosamine-related catabolic genes. The results allowed us to devise a new strategy for activating pathways for secondary metabolite biosynthesis. Such 'cryptic' pathways are abundant in actinomycete genomes, thereby offering new prospects in the fight against multiple drug-resistant pathogens and cancers.