Rhodococcus jostii RHA1: biology and applications

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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.