Genome Mining

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Big pharmaceutical companies made a mistake in giving up using soil bacteria as a source of antibiotics, say researchers who have now used 'genome mining" for finding new natural products that may have help in the treatment of superbug Methicillin-resistant Staphylococcus aureus (MRSA) and cancer.

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for difficult-to-treat infections in humans. It may also be referred to as multiple-resistant Staphylococcus aureus or oxacillin-resistant Staphylococcus aureus (ORSA).

"Over the last eight years we have been looking for new natural products in the DNA sequence of the antibiotic-producing bacterium Streptomyces coelicolor. In the last 15 years it became accepted that no new natural products remained to be discovered from these bacteria. Our work shows this widely-held view to be incorrect," said Professor Gregory Challis from the University of Warwick.

After the discovery of penicillin in 1928, there have been no rediscovery of known natural products. This led to technical challenges, which forced pharmaceutical companies to retreat and stop looking for new molecules.

But now, the complete genetic sequences of more than 580 microbes are known, which enables the researchers to identify pathways that produce new compounds by looking at the DNA sequences and many gene clusters likely to encode natural products have been analysed. 'Genome mining' has become a dynamic and rapidly advancing field.

The researchers have found the products of two cryptic gene clusters, of which, one was found to produce several compounds that inhibit the proliferation of certain bacteria. However, three of these compounds were new ones, named isogermicidin A, B and C.

"This discovery was quite unexpected. Our research provides important new methodology for the discovery of new natural products with applications in medicine, such as combating MRSA infections," said Professor Challis.

They also discovered one more product, which is called coelichelin. The researchers indicated that iron is essential for the growth of nearly all micro-organisms. But, despite being the fourth most abundant element in the Earth's crust it often exists in a ferric form, which microbes are unable to use.

"The gene cluster that directs production of coelicehlin was not known to be involved in the production of any known products. Our research suggests that coelichelin helps S. coelicolor take up iron," said Professor Challis.

In fact, a number of researchers have followed Professor Challis and his colleagues into the exciting field of genome mining.

"In the near future, compounds with useful biological activities will be patented and progressed into clinical or agricultural trials, depending on their applications" said Professor Challis.

The study is published in the latest issue of Microbiology