New Method Can Increase Commercial Antibiotic Yields

Mervyn Bibb (John Innes Centre)

Researchers from the U.K. and Japan have devised a new method for increasing the yields of antibiotic compounds from bacteria. The process, which has practical applications in commercial pharmaceutical production, is scheduled to be described this week in an online issue of the journal Proceedings of the National Academy of Sciences.

Most known antibiotics are produced naturally by soil bacteria called Streptomyces. For commercial production of these antibiotics, the natural production of antibiotics is increased by inducing mutations and screening for strains that show increased production, a hit-or-miss process that can take many years. As technology developed, these more productive strains were found to generate repeated copies of the genes needed for antibiotic production.

Molecular biologist Mervyn Bibb (pictured right) at the John Innes Centre in Norwich, U.K. and Koji Yanai with Meiji Seika Kaisha Ltd., a pharmaceutical company in Kanagawa, Japan, discovered 36 such repeating copies of one gene cluster in a strain of Streptomyces that had been repeatedly selected to over-produce the antibiotic kanamycin, used to treat serious bacterial infections.

Bibb and Yanai then identified the Streptomyces components responsible for the repeating clusters that led to kanamycin overproduction: two DNA sequences that flank the gene cluster, and a protein, known as ZouA, that recognizes the two sequences and replicates them. Those findings were published in April 2011 in the Journal of Bacteriology (paid subscription required).

In the new article, Bibb, Yanai, and colleagues from Japan and Canada describe a system for amplifying the gene clusters. The researchers genetically packaged the components, and then inserted them into Streptomyces coelicolor, another strain of Streptomyces. This step helped Streptomyces coelicolor over-produce actinorhodin, a blue-pigmented antibiotic compound.

The researchers believe this process will work with Streptomyces strains and antibiotics, as well as other unrelated bacteria, such as E. coli. As more bacteria genomes are sequenced, the researchers say this approach can also identify other gene clusters with heretofore unknown properties that can be developed into entirely new compounds.

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