Researchers have discovered a new microbial natural product by a technique called "genome mining," according to a paper in the October issue of Nature Chemical Biology. Using microbial DNA sequences, the authors predicted the existence and properties of a compound called coelichelin, isolated it from the microbe, and revealed its chemical structure. This technique shows the predictive power of genome mining for uncovering new natural products, which may speed the discovery of new medicines.
In the past, natural products chemists have unearthed many compounds from natural sources that have important medicinal properties. But this process involves laborious purification steps to find a desired small-molecule needle in a metabolite haystack. Gregory Challis and colleagues report a more predictive and streamlined approach based on genome mining. Using genome sequences from Streptomyces coelicolor, the authors identified biosynthetic gene clusters that helped them predict the existence of a previously unknown molecule, which they called coelichelin. Using this insight from genome sequences, the authors isolated coelichelin from the microbe.
Further structural detective work revealed that coelichelin is a tetrapeptide, which helps microbes acquire iron ions from their environment under iron-poor conditions. The authors also showed that the biosynthesis of this molecule is more complex than expected; it is produced by a three-component enzyme system working in concert with a separate protein, which is highly unusual for this class of compounds.
This innovative approach to isolating natural products suggests that genome mining may offer an alternative route to identifying new compounds of biological origin.
Gregory L. Challis (University of Warwick, Coventry, UK)
Additional contact for comment on paper:
Brian Bachmann (Vanderbilt University, Nashville, TN, USA)
Abstract available online.
(C) Nature Chemical Biology press release.
Message posted by: Trevor M. D'Souza