Rhodococcus jostii RHA1: biology and applications

乔斯红球菌 RHA1：生物学和应用

• 批准号: 121909-2010
• 负责人: Davies, Julian
• 金额: $ 2.4万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=451622
• 关键词: Rhodococcus; jostii; RHA1; biology; applications

Bacteria are very important to humankind in many respects. Most importantly, our health and survival is dependent on the bacterial populations in and on our body. We employ bacteria in many industries such as food, health, chemical, and environmental clean-up; many microbial products are used routinely. Among the most important are antibiotics that are the cornerstone of infectious disease treatment. Unfortunately, the useful lifetime of antibiotics is limited by the ability of microbes to become resistant to them and there is a need to find new and effective antibiotics. This proposal will take advantage of advances in molecular genetics to discover and produce novel types of antibiotics. Most of the antibiotics we use are produced by bacteria of the Actinomycete family and recent work on genome sequencing has shown that most strains of this genus have the potential to produce 20 or more antibiotics, however these compounds are not available because they are made by "silent" or "cryptic" pathways in Actinomycete strains. One approach to obtaining these compounds is to remove the biosynthetic clusters from their natural host and make them in heterologous hosts using defined expression systems that can be tailored to make the compounds in quantity. We have chosen to use Rhodococci as such a host; these bacteria grow fast and can be easily engineered to make robust hosts for antibiotic production. In order to achieve this goal we will to carry out detailed growth studies of different Rhodococcal strains to optimise growth conditions and to improve their abilities to produce antibiotics by various methods such as "ribosome engineering" The availability of such a collection of reliable host strains will permit the discovery of many novel compounds that should have useful antibiotic and other therapeutic applications.

细菌在许多方面对人类非常重要。最重要的是，我们的健康和生存取决于我们体内和体外的细菌数量。我们在食品、健康、化学和环境清理等许多行业中使用细菌;许多微生物产品是常规使用的。其中最重要的是抗生素，它是传染病治疗的基石。不幸的是，抗生素的使用寿命受到微生物对其产生耐药性的能力的限制，因此需要找到新的有效抗生素。该提案将利用分子遗传学的进步来发现和生产新型抗生素。我们使用的大多数抗生素是由放线菌科的细菌产生的，最近的基因组测序工作表明，该属的大多数菌株具有产生20种或更多种抗生素的潜力，然而这些化合物是不可用的，因为它们是通过放线菌菌株中的“沉默”或“隐蔽”途径产生的。获得这些化合物的一种方法是从其天然宿主中除去生物合成簇，并使用可定制以大量制备化合物的限定表达系统在异源宿主中制备它们。我们选择使用红球菌作为这样的宿主;这些细菌生长迅速，并且可以很容易地进行改造，成为抗生素生产的强大宿主。为了实现这一目标，我们将对不同的红球菌菌株进行详细的生长研究，以优化生长条件，并通过各种方法（如“核糖体工程”）提高其生产抗生素的能力。这种可靠的宿主菌株的收集的可用性将允许发现许多新的化合物，这些化合物应该具有有用的抗生素和其他治疗应用。