Transcriptional synergism in Acinetobacter

这些研究主要集中在土壤细菌不动杆菌sp. ADP1对芳香族化合物的降解。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，它们复杂的管理方案可以用于生物技术。在这个项目中，突变方法将解决转录控制中新型协同作用的分子基础。BenM是一种lysr型的苯甲酸盐分解代谢转录调节剂，对两种代谢物产生协同反应。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对效应物的反应是很重要的，因为它是细菌中最大的同源调节剂群体之一的关键代表。与x射线晶体学家Cory Momany博士的成功合作，获得了BenM和另一个类似物CatM的效应结合域的良好表征的原子水平结构。持续的生理学研究将检验新的调控模型。BenM和CatM之间的比较研究为确定控制效应调控转录的序列提供了独特的机会。虽然这两种调节因子在序列上相似，并且对代谢物顺式、顺式-苯甲酸盐起反应，但只有BenM对苯甲酸盐有额外的反应。BenM和CatM在调控上的重叠将被用来分析蛋白质及其靶DNA启动子中序列的功能意义。这些研究将阐明复杂的调控回路。学生将在一个重要的多学科领域进行培训，连接微生物生理学和结构生物学。了解lysr型调节因子对生物修复和生物技术具有广泛的意义，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.