Rational engineering of antibiotic production

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The "Streptomyces" bacteria exhibit a complex "secondary" or non-essential metabolism, producing small molecules called "natural products". As part of this process, the streptomycetes produce chemotherapeutic agents, anti-fungal drugs, immune suppressants used to prevent transplant rejection, herbicides, anti-helminthic drugs, and most notably the majority of the antibiotics in current clinical and agricultural use. New species of Streptomyces are easy to isolate from the soil but their secondary metabolites are produced in minute quantities under laboratory conditions: many cannot be detected at all. Research into secondary metabolism has provided us with a list of genes that, if over-expressed, could dramatically increase secondary metabolism. Our goal is to exploit these genes to produce "universal activators" of antibiotic production that can be used to maximize output in any streptomycete. In partnership with JNE Biotech Inc. we will develop this resource for use in the enhanced production of known drugs and the discovery of new drugs. Our short term goals are to 1. identify as many of the genes in the species S. coelicolor and S. griseus that can stimulate increased antibiotic production and 2. find ways of amplifying production of streptomycin and spectinomycin, and eventually other antibiotics, chemotherapeutic agents and anti-parasitic drugs produced by streptomycetes. Over the longer term we aim to apply these tools in uncharacterised streptomycetes to identify new agents capable of inhibiting/killing infectious microbes, parasites and tumour cells. This work will strengthen the Streptomyces research field by increasing our understanding antibiotic production. Benefits to Canada from this work will include the training of graduate students and postdoctoral fellows in sophisticated recombinant DN A and mass spectrometry technology. Furthermore, by enhancing our ability to produce known antibiotics and discover new secondary metabolites, we will strengthen biotechnology in Canada and facilitate the growth of a local biotechnology company (JNE Biotech Inc.). This will result in increased employment in the pharmaceutical sector in Hamilton.