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. It could also be valuable in helping to discover new compounds. With the ever-growing threat from antibiotic resistance, these tools will be very useful in ensuring that we have enough of these useful compounds in the future.
The majority of antibiotics we know of today are produced naturally by a group of soil bacteria called Streptomyces. For commercial production of these antibiotics for clinical use, it is necessary to increase the yield. This has typically been achieved by randomly inducing mutations and screening for strains that show increased production, a process that takes many years. When technology had progressed sufficiently to analyse how this had been achieved scientists found that, in some cases, the increase in yield was due to repeated copies of the genes needed for antibiotic production.
In almost all cases, the genes needed to produce these antibiotics are clustered together in the bacterial genome. In work carried out initially at the John Innes Centre, which is strategically funded by the Biotechnology and Biological Sciences Research Council, Professor Mervyn Bibb and collaborator Dr Koji Yanai from a Japanse laboratory discovered 36 repeating copies of one gene cluster in a strain of Streptomyces that had been repeatedly selected to over-produce the antibiotic kanamycin.
"This suggested to us that controlled and stable amplification of antibiotic gene clusters might be possible, and that if it was, it would be a valuable tool for engineering high yielding commercial strains of bacteria," said Prof Bibb. The researchers then went on to identify the components within Streptomyces responsible for creating the 36 repeating clusters that led to kanamycin overproduction. These consist of two DNA sequences that flank the gene cluster, and a
|Contact: Andrew Chapple|
Norwich BioScience Institutes