中文摘要
梭菌在碳循环、人体生理中扮演重要角色,在生物能源与生物炼制方面具有非常重要的应用潜力。如果要实现对梭菌代谢功能的理性设计与改造,需要理解代谢途径的分子调控机制。然而,目前我们对梭菌代谢的转录调控还知之甚少。基因组学的迅速发展为理解与认识梭菌转录调控的机制、组分以及功能,提供了丰富的背景信息。本项目拟利用比较基因组学技术重构梭菌中碳水化合物、氨基酸、核苷酸、辅因子等代谢相关转录因子和调节RNA的调节子(regulon),并对若干重要转录因子进行实验鉴定,阐明它们控制代谢途径上关键基因表达的机制,揭示其对产溶剂梭菌生理与代谢的调控作用,提高对梭菌转录调控网络和代谢网络之间关系的认识,逐步解决梭菌代谢功能的调控机制这一科学问题,为高效梭菌细胞工厂的建造提供理论基础,为病原性梭菌的防治、以及人类肠道菌群与疾病相关性等研究提供重要信息。
英文摘要
Organisms of the genus Clostridium are of great importance to the carbon cycle, human normo- and pathophysiology, but also in biofuel and biorefinery applications. Despite their fundamental and applied significance, the regulatory networks remain largely unexplored at the systems level. A large and growing number of complete genomes of Clostridium species allows us to gain insights into mechanisms, components, and behavior of the complex, multilayered transcriptional regulatory machinery in clostridia. In this study we will combine comparative genomics with experimental techniques to reconstruct transcriptional regulons involved in the metabolism of carbohydrates, amino acids, nucleotides, cofactors in clostridia. The mechanisms of key transcription factors controlling expression of important metabolic genes will be elucidated. The roles of these regulators in physiology and metabolism of solvent-producing clostridia will be revealed. This study will greatly improve our understanding of metabolic regulatory mechanisms in clostridia, which is important for bioengineering and biomedical applications of Clostridium species.
