Directed Evolution of Glycosyltransferases

糖基转移酶的定向进化

• 批准号: 6884993
• 负责人: Kerry R Love
• 金额: $ 4.21万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6884993
• 关键词: active sites; antibiotics; biotechnology; chimeric proteins; directed evolution; drug design /synthesis /production; drug resistance; enzyme activity; enzyme substrate; glycopeptides; glycosylation; glycosyltransferase; high performance liquid chromatography; method development; phage display; polymerase chain reaction; postdoctoral investigator; uridine diphosphate glucose; vancomycin

DESCRIPTION (provided by applicant): The increasing incidence of antibiotic resistant bacterial infections indicates the need for improved constructs to treat enterococcal infected patients. Modification of existing glycopeptide antibiotics, such as vancomycin and teicoplanin, on and around the sugar substitutents has led to the clinical trials of new treatments, including oritavancin. The long-term goal of this research is to develop an improved understanding of the active-site selectivity of glycosyltransferases so that new, non-native carbohydrate-based constructs may be identified for treatment of drug-resistant infections. The specific question addressed in the context of this research is: "How is the native enzyme active site modified in a mutant glycosyltransferase that is capable of glycosylating a non-native substrate?" This research will develop an existing tool in molecular biology, phage display, for the molecular evolution of mutant glycosyltransferases. We believe that identifying enzymes that can glycosylate new substrates will segue into the generation of catalysts able to compete with chemical synthesis for the rapid and large scale production of glycoconjugates.

描述（由申请人提供）：