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06 September 2011John Innes Centre / PNAS
Novel method for increasing antibiotic yields
A novel way of increasing the amounts of antibiotics produced by bacteria has been discovered that could markedly improve the yields of these important compounds in commercial production. In work carried out initially at John Innes Centre scientists recently discovered 36 repeating copies of one gene cluster in a strain of Streptomyces that had been repeatedly selected to over-produce the antibiotic kanamycin. Published in the journal Proceedings of the National Academy of Sciences, researchers now describe a system for the targeted amplification of these gene clusters.
The majority of antibiotics we know of today are produced naturally by a group of soil bacteria calles Streptomyces. In almost all cases, the genes needed to produce antibiotics are clustered together in the bacterial genome. The researchers were able to engineer these gene clusters into genetic 'cassettes' and then insert these into another strain of Streptomyces. They successfully used the system to make Streptomyces coelicolor overproduce actinorhodin, a blue-pigmented antibiotic. They believe the system will work equally as well for many other Streptomyces strains and antibiotics, and have also shown that it functions in an unrelated bacterium, Escherichia coli.
The system may also uncover new, undiscovered antibiotics. A number of Streptomyces species have had their entire genomes sequenced, and many more are expected. Researchers have been able to identify other gene clusters within these sequences with unknown products. It is likely that many of these 'cryptic' gene clusters produce potentially new antibiotics, but at an undetectable level, or only under specific environmental conditions. Using the gene cluster amplification system identified here, it will be possible to amplify these cryptic gene clusters, identify their products, and potentially discover new antibiotics for the battle against resistant superbugs.
Murakami et al. A novel system for the amplification of bacterial gene clusters multiplies antibiotic yield in Streptomyces coelicolor. PNAS Early Edition. doi: 10.1073/pnas.1108124108
