Data from: 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-independent CCR. Deletion of glkA led to strong downregulation of biosynthetic proteins for prodigionin and calcium-dependent antibiotic (CDA) in mannitol-grown cultures. Repression of bldB, bldN, and its target bldM explains the poor development of S. coelicolor on solid-grown cultures containing glucose. A new model for carbon catabolite repression in streptomycetes is presented.栖息于土壤的原核生物链霉菌属（Streptomyces）成员对于复杂多糖的循环利用不可或缺，同时可合成种类繁多的天然产物。养分可利用性是链霉菌转向发育阶段与抗生素合成的核心调控因素。碳分解代谢物阻遏（Carbon catabolite repression, CCR）作为介导该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（Glucose kinase, Glk）。本研究借助可对约2000种蛋白质（几乎涵盖所有中心代谢相关酶类）的表达水平进行比较的高级蛋白质组学技术，为天蓝色链霉菌（Streptomyces coelicolor）中存在全新的Glk非依赖型CCR通路提供了实验证据。尽管初级代谢与次级代谢酶类的CCR效应、诱导物排阻作用，以及天然产物前体供给大多通过Glk介导，但尿素循环相关酶类，以及γ-丁内酯Scb1与响应性隐性聚酮Cpk的生物合成酶类，却受到Glk非依赖型CCR的调控。在甘露醇培养的菌株体系中，glkA基因的敲除会导致灵菌红素（prodigionin）与钙依赖性抗生素（CDA）的生物合成蛋白质被显著下调。bldB、bldN及其靶基因bldM的表达受抑制，可解释天蓝色链霉菌在含葡萄糖的固体培养基中发育不良的现象。本研究提出了链霉菌中碳分解代谢物阻遏的全新调控模型。