Coordination Funds

蓝藻中的自养-异养开关：多个调节层的一致决策简称：SCyCode(开关在蓝藻中：一致决策)蓝藻是地球上最原始的产氧光合作用生物。它们突出的生态影响是建立在新陈代谢的基础上的，新陈代谢将二氧化碳和水转化为有机物质，同时仅使用光能释放氧气。最近，人们越来越多地将蓝藻作为可持续经济的细胞工厂进行研究。尽管它们在全球环境和经济上的重要性不断上升，但我们对它们初级新陈代谢的调节知识是支离破碎的，这也是由于新陈代谢的高度复杂性。蓝藻在昼夜循环或特定的环境条件下，在光自养和异养代谢模式之间切换，两种生活方式的酶能力都存在于一个细胞中。为了破译调控和操作这些过程的分子机制，一个涵盖相关专业知识的跨学科团队联合起来，成立了研究单位“蓝藻中的自养异养开关：多个调节层上的一致决策”(缩写为“SCyCode”)。在第一个资助期取得的重大发现突出了同工酶在多个层面上调节的重要性，例如受氧化还原或能量状态、翻译后蛋白质修饰或更高阶多酶复合体的动态自组织调节的重要性，其中涉及非酶调节多肽，如CP12或新发现的PirC和NblD多肽。此外，SCyCode还建立了用于分析多亚基蛋白质代谢物和蛋白质-RNA复合体的资源，社区已经可以通过适当的数据库获取这些资源。我们的联盟还启动了对蓝藻磷酸蛋白质组、代谢组和蛋白质组的系统了解的主要步骤。通过跟踪不同生长条件和生理状态下主要大分子络合物的组成和修饰的动态变化，这些资源将在第二个资助期内得到大幅扩展。基于第一个资助期的结果，我们提出了一些假设，我们将在第二个资助期的具体实验中对这些假设提出质疑。一个主要的重点将是将在机械水平上获得的洞察力与对途径组织和调控、氧化还原信号和翻译后控制机制的结构-功能理解相结合，这将最终形成蓝藻初级代谢的综合动力学模型。这种对负责代谢开关的网络控制的综合观点对于未来的生物技术应用以及对蓝藻新陈代谢及其调控的系统水平的理解是至关重要的。

The Autotrophy-Heterotrophy Switch in Cyanobacteria: Coherent Decision-Making at Multiple Regulatory LayersShort title: SCyCode (Switch in Cyanobacteria: Coherent decision-making)Cyanobacteria are the primordial oxygenic photosynthetic organisms on Earth. Their outstanding ecological impact is based on a metabolism, which converts carbon dioxide and water into organic material with the concomitant release of oxygen only using light energy. Recently, cyanobacteria are increasingly investigated as cell factories for a sustainable economy. Despite their global environmental and rising economic importance, our knowledge on the regulation of their primary metabolism is fragmented, which is also due to the unforeseen high complexity of metabolism. Cyanobacteria switch between photoautotrophic and heterotrophic modes of metabolism during day/night cycles or under specific environmental conditions with the enzymatic capacity for both life-styles being present in one cell. To decipher the molecular mechanisms regulating and operating these processes, an interdisciplinary team that covers the relevant expertise joined forces by establishing the research unit “The Autotrophy Heterotrophy Switch in Cyanobacteria: Coherent decision-making on multiple regulatory layers” (abbreviated “SCyCode”). Major discoveries achieved during the first funding period highlight the importance of isoenzymes regulated at multiple layers, for example by the redox or energy state, by post-translational protein modifications, or by the dynamic self-organization of higher order multi-enzyme complexes, which involves non-enzymatic regulatory peptides such as CP12 or the newly discovered PirC and NblD peptides. Furthermore, SCyCode has established resources for the analysis of multi-subunit protein–metabolite and of protein-RNA complexes that can already be accessed by the community through suitable databases. Our consortium has also initiated major steps for the systematic understanding of the cyanobacterial phosphoproteome, metabolome and proteogenome. These resources will be substantially extended during the second funding period by following the dynamic changes in the composition and modification of major macromolecular complexes through different growth conditions and physiological states. Based on the results from the 1st funding period, hypotheses have been developed which we will challenge in specific experiments during the second funding period. A major focus will be combining the obtained insight at mechanistic levels with a structure-function understanding of pathway organization and regulation, redox signalling, and posttranslational control mechanisms, which will culminate in an integrative kinetic model for cyanobacterial primary metabolism. Such an integrated view on the network control responsible for metabolic switches is essential for future biotechnological applications as well as a system level understanding of cyanobacterial metabolism and its regulation.