Transcriptional synergism in Acinetobacter

这些研究的重点是芳香族化合物降解土壤细菌不动杆菌属ADP 1。微生物分解代谢途径是研究生物化学、遗传学和生理学的良好系统。此外，它们复杂的管理制度可用于生物技术。在这个项目中，突变的方法将解决一个新的协同作用在转录控制的分子基础。BenM是苯甲酸催化剂的LysR型转录调节因子，其协同响应于两种代谢物。一种蛋白质整合多种细胞信号的能力可以影响基因表达的快速和大的变化。了解BenM对效应子的反应很重要，因为它是细菌中最大的同源调节子组之一的关键代表。与X射线晶体学家Cory Momany博士的成功合作，产生了BenM和另一种paradox CatM的效应器结合结构域的原子水平结构。持续的生理学研究将测试新的调节模型。BenM和CatM之间的比较研究提供了独特的机会，以确定控制效应调控转录的序列。虽然这两种调节剂的序列相似，并响应于代谢产物顺式，顺式-粘康酸，只有BenM响应额外的苯甲酸。BenM和CatM之间的调控重叠将用于剖析蛋白质及其靶DNA启动子中序列的功能意义。这些研究将阐明复杂的调节回路。学生将在一个重要的多学科领域的桥梁微生物生理学和结构生物学的培训。了解LysR型调节剂对生物修复和生物技术具有广泛的意义，包括开发生物传感器来检测有害化合物。

These studies focus on aromatic compound degradation by the soil bacterium Acinetobacter sp. ADP1. Microbial catabolic pathways are good systems for studying biochemistry, genetics, and physiology. Moreover, their complex regulatory schemes can be exploited for biotechnology. In this project, mutational approaches will address the molecular basis of a novel synergism in transcriptional control. BenM is a LysR-type transcriptional regulator of benzoate catabolism that responds synergistically to two metabolites. The ability of one protein to integrate multiple cellular signals can effect rapid and large changes in gene expression. Understanding the response of BenM to effectors is important because it is a key representative of one of the largest groups of homologous regulators in bacteria. A successful collaboration with an X-ray crystallographer, Dr. Cory Momany, yielded well-characterized atomic level structures of the effector-binding domains of BenM and another paralog, CatM. Continued physiological investigations will test new regulatory models. Comparative studies between BenM and CatM provide unique opportunities to determine sequences that govern effector-regulated transcription. Although both regulators are similar in sequence and respond to the metabolite cis,cis-muconate, only BenM responds additionally to benzoate. The overlap in regulation between BenM and CatM will be used to dissect the functional significance of sequences in the proteins and in their target DNA promoters. These studies will elucidate complex regulatory circuits. Students will be trained in an important multidisciplinary area bridging microbial physiology and structural biology. Understanding LysR-type regulators has broad relevance for bioremediation and biotechnology, including the development of biosensors to detect harmful compounds.