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: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=522232
• 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，我们的健康和生存依赖于体内和体内的细菌种群。我们在许多行业使用细菌，如食品、健康、化工和环境清理；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抗药性的能力的限制，因此需要寻找新的有效抗生素。这项提议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都是由放线菌家族的细菌产生的，最近的基因组测序工作表明，这个属的大多数菌株都有可能产生20种或更多的抗生素，但这些化合物是不可用的，因为它们是由放线菌菌株中的“沉默”或“隐蔽”途径产生的。获得这些化合物的一种方法是从它们的自然宿主中去除生物合成簇，并使用定义的表达系统使它们处于异源宿主中，该表达系统可以定制以制造大量的化合物。我们选择使用红球菌作为这样的宿主；这些细菌生长迅速，可以很容易地被改造成强大的宿主，用于抗生素生产。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)提高它们生产抗生素的能力。提供这样一组可靠的宿主菌株将使我们能够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。