Transcriptional synergism in Acinetobacter

这些研究重点是土壤细菌不动杆菌对芳香族化合物的降解。 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，它们复杂的监管方案可用于生物技术。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 是苯甲酸分解代谢的 LysR 型转录调节因子，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 对效应子的反应非常重要，因为它是细菌中最大的同源调节因子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 和另一种旁系同源物 CatM 效应子结合域的良好表征的原子级结构。持续的生理学研究将测试新的监管模型。 BenM 和 CatM 之间的比较研究为确定控制效应调节转录的序列提供了独特的机会。尽管两种调节剂的序列相似并且对代谢物顺式粘康酸有反应，但只有 BenM 对苯甲酸盐有额外的反应。 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。学生将在连接微生物生理学和结构生物学的重要多学科领域接受培训。了解 LysR 型调节剂与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.