AsianScientist (Sep. 11, 2011) – An international team of scientists has developed a method for making multiple copies of specific clusters of genes in bacteria, a process which can be used to increase the amounts of antibiotics produced by bacteria.
Most antibiotics are produced naturally by a group of soil bacteria called Streptomyces. In commercial production of antibiotics, increased yields from bacteria are required to satisfy the demand for antibiotics in the clinic.
This has typically been achieved by randomly inducing mutations and screening for strains that show increased production, a process that takes many years.
The researchers discovered that, in some cases, the increase in yield can be attributed to the bacteria having multiple copies of the genes needed for antibiotic production.
In their paper, published in the Proceedings of the National Academy of Sciences, they reported that a strain of Streptomyces repeatedly selected to over-produce the antibiotic kanamycin had 36 repeating copies of the gene cluster needed to produce the antibiotic.
The researchers 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 protein, known as ZouA, that recognizes the two sequences and replicates them.
The researchers were able to engineer these components into genetic ‘cassettes’ and then insert these into another strain of Streptomyces. Using this system, they successfully engineered Streptomyces coelicolor to overproduce actinorhodin, a blue-pigmented antibiotic.
They believe the system will work equally well for other Streptomyces strains and antibiotics, and have also shown that it functions in an unrelated bacterium, Escherichia coli.
The article can be found at: Murakami T et al. (2011) A system for the targeted amplification of bacterial gene clusters multiplies antibiotic yield in Streptomyces coelicolor.
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Source: Norwich BioSciences Institutes.
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