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Antibiotic Regulatory Genes and Metabolic Engineering

抗生素调控基因与代谢工程

基本信息

批准号：
6555840
负责人：
ANDREW R REEVES
金额：
$ 31.8万
依托单位：
FERMALOGIC, INC.
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-15 至 2003-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6555840
关键词：
Actinomycetales bacterial genetics biological products biotechnology erythromycin gene mutation gene targeting genetic library genetic screening genetic strain microorganism mass culture microorganism metabolism plasmids regulatory gene

项目摘要

DESCRIPTION (provided by applicant): Strain improvement of commercial fermentations helps to reduce the cost of production of existing pharmaceuticals and helps industry to meet the growing demands for desperately needed new products, such as antibiotics, that can be produced in large enough quantities and at prices the public can afford. This project focuses on strain improvement in a bacterium that generates a widely used antibiotic, erythromycin. This bacterium, Saccharopolyspora erythraea, is a member of the Actinomycete family and is widely used in academic research and industry, making it an excellent model system for this work. The objective of this project is to identify and manipulate genes responsible for controlling erythromycin yield during fermentation. In Phase I a mutagenic plasmid insertion library was created in Sac. erythraea and four classes of morphological and pigmentation mutants were found using a simple visual screen. Three classes of mutants were found that showed significant increases in erythromycin production. An efficient plasmid rescue technique allowed recovery of the integrated plasmid and DNA sequence analysis of the plasmid insert. In Phase II the screening and mutant analysis will continue. The strain improvement genes found could have general application to strain improvement programs for other drugs. PROPOSED COMMERCIAL APPLICATION: Not Available

描述（由申请人提供）：商业菌株的菌株改良发酵有助于降低现有产品的生产成本药品并帮助行业满足日益增长的迫切需求需要能够大规模生产的新产品，例如抗生素数量和价格是公众可以承受的。该项目重点关注应变改进产生广泛使用的抗生素的细菌，红霉素。这种细菌，红糖多孢菌，是放线菌家族并广泛应用于学术研究和工业领域，使其成为这项工作的优秀模型系统。此举的目的项目是识别和操纵负责控制的基因发酵过程中红霉素的产量。在第一阶段，诱变质粒插入文库是在 Sac 中创建的。红斑和四类使用简单的视觉屏幕发现了形态和色素沉着突变体。发现三类突变体，显示出显着增加红霉素生产。有效的质粒救援技术可实现康复整合质粒和质粒插入片段的 DNA 序列分析。在第二阶段的筛选和突变体分析将继续进行。应变发现的改良基因可普遍应用于菌株改良其他药物的计划。拟议的商业应用：无法使用