Transcriptional synergism in Acinetobacter

这些研究主要集中在土壤细菌不动杆菌降解芳香族化合物方面。ADP1。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，他们复杂的监管方案可以被用于生物技术。在这个项目中，突变方法将解决转录控制中一种新的协同作用的分子基础。BenM是苯甲酸分解代谢的LysR型转录调节因子，对两种代谢物有协同作用。一种蛋白质整合多个细胞信号的能力可以影响基因表达的快速和大规模变化。了解BenM对效应器的反应是重要的，因为它是细菌中最大的同源调控因子之一的关键代表。与X射线结晶学家Cory Momany博士的成功合作，产生了BenM和另一种Paralog CATM效应器结合结构域的良好表征的原子级结构。持续的生理研究将测试新的调控模式。BenM和CATM之间的比较研究为确定控制效应器调控转录的序列提供了独特的机会。虽然这两种调节剂在序列上相似，并对代谢产物顺式-松果酸做出反应，但只有苯甲基对苯甲酸有额外的反应。BenM和CATM在调控上的重叠将被用来剖析蛋白质及其靶DNA启动子中序列的功能意义。这些研究将阐明复杂的调节电路。学生将在一个重要的多学科领域接受培训，该领域是微生物生理学和结构生物学的桥梁。了解LysR类调节剂对生物修复和生物技术具有广泛的相关性，包括开发检测有害化合物的生物传感器。

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.