S MUTANS--CHARACTERIZATION OF ITS MUTACIN ANTIBIOTIC

S mutans--其突变蛋白抗生素的表征

• 批准号: 6379648
• 负责人: PAGE W CAUFIELD
• 金额: $ 0.78万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379648
• 关键词: DNA footprinting; Streptococcus mutans; antibiotics; bacterial genetics; bacterial proteins; gel mobility shift assay; gene expression; genetic manipulation; genetic promoter element; northern blottings; nuclear magnetic resonance spectroscopy; operon; oral bacteria; peptides; protein biosynthesis; protein engineering; protein structure function; reporter genes; site directed mutagenesis; yeast two hybrid system

DESCRIPTION (Adapted from the investigator's Abstract): The proposed research is an extension of previous research pursuing the discovery of a novel antibiotic elaborated by the oral cariogenic bacterium Streptococcus mutans. This potent antibiotic, called mutacin, is a member of the growing class of bacterially synthesized peptide antibiotics called lantibiotics. Lantibiotics are ribosomally synthesized and post-translationally modified peptides containing unusual amino acids called lanthionines, and are produced by, and primarily act on, gram-positive bacteria. Because the mutacin peptide and other lantibiotics are DNA-encoded, changes in their expression and composition can be accomplished by site-directed mutagenesis. For example, genetically-engineered analogues of the nascent mutacin molecule can be modified for an enhanced spectrum of activity against specific pathogens. The aims of the present research are to define and characterize the genetic and biochemical aspects of mutacin biosynthesis, to document its antimicrobial activities, and to study the factors involved with the regulation of its production. Taking advantage of a rapidly growing repertoire of molecular biological techniques including site-directed and cassette mutagenesis, each component of the mutacin molecule can be manipulated and its role determined. From this information, the production of mutacin may be enhanced by genetic and protein engineering. It is anticipated that, at the end of the next five years, the genetic and biochemical determinants for mutacin will be understood and significant progress made towards the large scale production for possible therapeutic application can be explored. Clearly, the race to find not only a targeted, specific antimicrobial against the etiological agents of dental caries, but also against the emerging group of drug resistant pathogens underpins the importance of this area of scientific pursuit.

描述（改编自研究者摘要）：拟定的 这项研究是以前研究的延伸， 由口腔致龋细菌链球菌制备的新型抗生素 变异人 这种被称为变他霉素的强效抗生素， 细菌合成的肽类抗生素，称为羊毛硫抗生素。 羊毛硫抗生素是核糖体合成和后修饰 肽含有不寻常的氨基酸称为羊毛硫氨酸， 由革兰氏阳性菌产生并主要作用于革兰氏阳性菌。 因为 突变素肽和其他羊毛硫抗生素是DNA编码的， 表达和组成可以通过定点诱变来完成。 例如，新生突变蛋白的基因工程类似物 分子可以被修饰以增强抗 特定病原体。 本研究的目的是定义和 表征变链蛋白生物合成的遗传和生物化学方面， 记录其抗菌活性，并研究相关因素 与其生产的规范。 利用快速 越来越多的分子生物学技术，包括 定点突变和盒式突变，突变蛋白的每个组分 分子可以被操纵并确定其作用。 从这些信息来看， 突变蛋白产生可以通过遗传和蛋白质 工程. 预计在今后五年结束时， 将理解突变蛋白的遗传和生物化学决定因素， 大规模生产取得了重大进展， 可以探索治疗应用。 很明显，这场竞赛不仅 一种针对牙科疾病病原体的靶向特异性抗菌剂， 龋齿，而且还对新出现的耐药病原体组 强调了这一科学领域的重要性。