Metabolic engineering of streptomyces

Kapitel i bok, 2009

Some of the common soil microorganisms are actinomycetes, Gram-positive bacteria with high GC content. Because of their mycelial habit they were initially believed to be fungi, which reected in their name (mucus (lat.) means fungus). In 1939, one year before rediscovery of penicillin by Florey and Chain, soil microbiologist Waksman has set his lab on a quest for new antimicrobial drugs. From the previous studies he knew that actinomycetes can inhibit the growth of other soil bacteria through secretion of bioactive compounds, which he named “antibiotics” (anti (lat.) against, bio (lat.) life). Systematic search for antibiotics produced by actinomycetes resulted in the discovery of actinomycin (1940), clavacin, and streptothricin (1942), all of them sadly turned out to be toxic in animal tests. In 1943 Waksman’s student Schatz isolated streptomycin-producing strain of Streptomyces griseus.1 Streptomycin was not particularly toxic to animals and humans, but remarkably was the rst compound active against tuberculosis bacteria. Many pharmaceutical companies and research laboratories started to collect soil samples from all over the world in search of antibiotics-producing organisms. Most of the discoveries were made in the rst ten years of the “hunt,” the larger part involved Streptomyces species. Streptomyces is a genus in the genera of actinomycetes, many of these bacteria produce volatile compounds that give the earth its characteristic odor. Streptomyces proved to be an excellent source of secondary metabolites, including antibiotics, anticancerous agents, antihelmintic drugs, and other useful compounds (Table 24.1). At present more than half of antibiotics in clinical use are produced in Streptomyces species.