Exploration of carbohydrate metabolism in hyperthermophilic archaea: novel approaches, enzymes and metabolic pathways

超嗜热古菌碳水化合物代谢的探索：新方法、酶和代谢途径

• 批准号: 381206548
• 负责人: Professor Dr. Markus Kaiser
• 金额: --
• 依托单位: Zentrum für Medizinische Biotechnologie (ZMB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/381206548?language=en
• 关键词: Exploration; carbohydrate; metabolism; hyperthermophilic; archaea

Archaea, the third domain of life, are characterized by unique biological traits such as a metabolism that shares bacterial and eukaryotic properties but also features unique pathways and enzymes. Among them, (hyper)thermophiles are particular interesting because these archaea are adapted to extreme environmental conditions (temperature, pH, etc.) that turn their enzyme repertoire into an intriguing source for the discovery of novel enzymes (accordingly often referred to as extremozymes) for biotechnological applications. A broader use of enzymes from (hyper)thermophilic archaea as well as molecular insights into their unique metabolic pathways is however currently hampered by a lack of suitable methodologies for their identification and systematic study.In this proposal, we want to establish and apply novel methodologies for overcoming these current bottlenecks. As a showcase, we will focus in our application on the glycosidase enzyme family as well as their corresponding carbohydrate degradation pathways. To this end, we will 1) establish activity-based protein profiling (ABPP) as a new approach for studying these enzymes and pathways in (hyper)thermophilic archaea, 2) apply ABPP and other methodologies such as transcriptomics, (meta)genomics and biochemical approaches to characterize these enzymes and pathways in three model strains with unusual properties in carbohydrate degradation, 3) isolate novel (hyper)thermophilic strains by in situ enrichment strategies and characterize them with our ABPP as well as the more established Polyomics and biochemical approaches and 4) define the scope of ABPP for chemical profiling of environmental community cultures. The proposed project thereby critically depends on the scientific collaboration between the Russian and German partners as both sides have complementary expertise and resources. The Russian partners are experts in isolation of novel (hyper)thermophilic strains and their characterization via (meta)genomics and transcriptomics while the German groups will complement with their biochemical as well as ABPP and proteomics expertise. We anticipate that the conjoint project will thus not only lead to novel insights in archaeal biology, biotechnology and ABPP but also provide the basis for extensive knowledge flow between both countries.

生命的第三个领域是微生物，其特征是独特的生物学特性，例如具有细菌和真核生物特性的代谢，但也具有独特的途径和酶。其中，（超）嗜热菌特别有趣，因为这些古菌适应极端环境条件（温度，pH值等）。这使得他们的酶谱成为一个有趣的来源，发现新的酶（因此通常被称为极端酶）的生物技术应用。然而，目前缺乏合适的方法来鉴定和系统研究嗜热古菌中的酶及其独特的代谢途径，从而阻碍了嗜热古菌酶的更广泛应用。在这项提议中，我们希望建立和应用新的方法来克服这些瓶颈。作为展示，我们将集中在我们的应用上的糖苷酶家族以及相应的碳水化合物降解途径。为此，我们将1）建立基于活性的蛋白质谱（ABPP）作为研究（超）嗜热古菌中这些酶和途径的新方法，2）应用ABPP和其他方法，如转录组学，（Meta）基因组学和生物化学方法来表征三种具有不寻常的碳水化合物降解特性的模式菌株中的这些酶和途径，3）通过原位富集策略分离新的（超）嗜热菌株，并用我们的ABPP以及更成熟的多聚体学和生物化学方法对其进行表征，以及4）定义ABPP用于环境群落培养物的化学分析的范围。因此，拟议的项目关键取决于俄罗斯和德国合作伙伴之间的科学合作，因为双方具有互补的专业知识和资源。俄罗斯合作伙伴是分离新型（超）嗜热菌株及其通过（Meta）基因组学和转录组学表征的专家，而德国团队将补充其生物化学以及ABPP和蛋白质组学专业知识。我们预计，这一联合项目不仅将带来古生物学、生物技术和ABPP方面的新见解，还将为两国之间的广泛知识流动提供基础。