Epsilon-变形菌氧气感知蛋白与应答因子的作用机制研究

从深海热液口到人体内都有分布的Epsilon-变形菌主要以微好氧和厌氧方式生存，因此氧气感知能力对它们适应环境变化发挥着重要功能。我们的生信分析发现这类细菌的基因组含有多拷贝的氧气感知蛋白—蚯蚓血红素蛋白。目前对该结构域感知氧气后引发的细胞应答过程包括它与其它结构域或蛋白的互作机制、信号转导模式和下游的信号输出的研究十分匮乏。我们在模式菌株中的初步研究发现一个含蚯蚓血红素结构域的蛋白与下游的转录调控因子存在共转录和蛋白-蛋白互作，是一种新型的氧气感知与应答调控模式。本项目拟对这两个蛋白开展功能研究，阐明两个蛋白之间的相互作用机制以及不同氧气浓度下两个蛋白如何调控靶基因表达作出生理响应。该研究将揭示一种新型的氧气感知与应答作用模式，为合成生物学的基因回路设计提供氧感知元件相关的理性设计原理，并且对Epsilon-变形菌纲的病原菌防治以及极端环境富集的细菌资源开发利用有重要指导作用。

Oxygen sensing plays an important role in the environmental adaptation of Epsilon-proteobacteria, which are mostly microaerophilic or anaerobic, widely distributed from deep-sea hydrothermal vent to human gut. Our comparative genomic analysis discovered that this group of bacteria encode multiple copies of oxygen-sensing domain such as hemerythrin. Several in vitro biochemical and structural analysis proved that this protein domain can bind oxygen. However, the cellular responses triggered by oxygen-binding of this protein remain elusive, including the interaction of this domain with other domains or proteins, signal transduction mode or signal outputs. To explore these questions, we studied a hemerythrin-containing protein and its cognate downstream regulator in a model strain. Our preliminary results indicate that these two proteins are co-transcribed and interact with each other, which are novel oxygen sensor and regulator pair. Thus, we propose to carry out functional studies on these sensor-regulator pair to elucidate their interaction mechanisms and how they affect cellular response to oxygen level. This study will reveal a new oxygen sensing and response mechanism, which will provide a useful oxygen sensor and working principles for gene circuit design in synthetic biology. Furthermore, this work will shed important insight into the bioprospecting of this group of bacteria abundant in extreme environment and also the control of bacterial pathogens.