Antibiotic production by Streptomyces clavuligerus

由微生物产生的抗生素是对抗传染病的主要防御手段，但其有效性正受到威胁。病原菌正在以惊人的速度对我们许多最有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。临床上使用的所有克拉维酸都来自于棒状链霉菌的发酵。研究克拉维酸的产生是为了了解参与其合成的生物合成酶的出现和消失是如何在S.棒形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。我们使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生物合成的细节。对调控基因的研究阐明了各种生物合成酶产生的条件。这些研究可能导致现有抗生素的更有效生产，或可能导致新型抗生素的开发。

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.