Identification of glucose kinase dependent and independent pathways for carbon control of primary metabolism, development and antibiotic production in Streptomyces coelicolor by quantitative proteomics

Members of the soil-dwelling prokaryotic genus Streptomyces are indispensable for the recycling of complex polysaccharides, and produce a wide range of natural products. Nutrient availability is a major determinant for the switch to development and antibiotic production in streptomycetes. Carbon catabolite repression (CCR), a main signaling pathway underlying this phenomenon, was so far considered fully dependent on the glycolytic enzyme glucose kinase (Glk). Here we provide evidence of a novel Glk-independent pathway in Streptomyces coelicolor, using advanced proteomics that allowed the comparison of the expression of some 2,000 proteins, including virtually all enzymes for central metabolism. While CCR and inducer exclusion of enzymes for primary and secondary metabolism and precursor supply for natural products is mostly mediated via Glk, enzymes for the urea cycle, as well as for biosynthesis of the γ-butyrolactone Scb1 and the responsive cryptic polyketide Cpk are subject to Glk-in...

栖息于土壤的原核生物属链霉菌（Streptomyces）成员在复杂多糖的循环降解中发挥不可或缺的作用，同时可合成种类繁多的天然产物。养分可获得性是链霉菌转向发育进程与抗生素合成的关键调控因素。碳分解代谢物阻遏（Carbon catabolite repression, CCR）作为介导该调控现象的核心信号通路，此前被认为完全依赖于糖酵解酶葡萄糖激酶（Glk）。本研究借助可实现约2000种蛋白质表达水平比较的高级蛋白质组学技术，在天蓝色链霉菌（Streptomyces coelicolor）中证实了一条全新的不依赖Glk的调控通路，该分析覆盖了几乎所有中心代谢相关酶类。研究结果显示，初级代谢、次级代谢相关酶以及天然产物前体供应相关的碳分解代谢物阻遏与诱导排斥效应大多由Glk介导；而尿素循环相关酶、γ-丁内酯Scb1的生物合成酶以及响应性隐性聚酮Cpk的调控则依赖于Glk-