Antibiotic production by Streptomyces clavuligerus

棒状链霉菌生产抗生素

• 批准号: 2824-2006
• 负责人: Jensen, Susan
• 金额: $ 6.04万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=361330
• 关键词: Antibiotic; production; Streptomyces; clavuligerus

Antibiotics produced by microbes are a main defense against infectious diseases, but their effectiveness is being threatened. Pathogenic bacteria are developing resistance to many of our most useful drugs at an alarming rate. Clavulanic acid is a beta-lactamase inhibitor that is widely used together with penicillin and cephalosporin antibiotics to overcome resistance mediated by production of beta-lactamases. All clavulanic acid used clinically comes from fermentations of the organism, Streptomyces clavuligerus. Production of clavulanic acid is being studied to understand how the appearance and disappearance of the biosynthetic enzymes involved in its synthesis is regulated in S. clavuligerus. The genes encoding these biosynthetic enzymes are spread across three gene clusters in the chromosome, and each gene cluster is regulated differently. We use mutagenesis and analysis of the resulting mutants to investigate the details of the biosynthesis of clavulanic acid biosynthesis. Studies on regulatory genes clarify the conditions under which the various biosynthetic enzymes will be produced. These studies could lead to more efficient production of existing antibiotics or possibly to the development of new types of antibiotics.

微生物产生的抗生素是预防传染病的主要手段，但其有效性正在受到威胁。致病菌正以惊人的速度对许多我们最常用的药物产生耐药性。克拉维酸是一种β -内酰胺酶抑制剂，广泛与青霉素和头孢菌素类抗生素一起使用，以克服由β -内酰胺酶产生介导的耐药性。所有临床使用的克拉维酸都来自于生物的发酵，克拉维酸链霉菌。目前正在研究clavulanic酸的生产，以了解在S. clavuligerus中参与其合成的生物合成酶的出现和消失是如何被调节的。编码这些生物合成酶的基因分布在染色体上的三个基因簇中，每个基因簇受到不同的调控。我们利用诱变和分析所产生的突变体来研究克拉维酸生物合成的细节。调控基因的研究阐明了各种生物合成酶产生的条件。这些研究可能导致更有效地生产现有抗生素或可能开发新型抗生素。