Genome Mining Reveals New Natural Products

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.

Author contact:

Gregory L. Challis (University of Warwick, Coventry, UK)
E-mail: g.l.challis@warwick.ac.uk

Additional contact for comment on paper:

Brian Bachmann (Vanderbilt University, Nashville, TN, USA)
E-mail: brian.o.bachmann@vanderbilt.edu

Abstract available online.

(C) Nature Chemical Biology press release.

Message posted by: Trevor M. D'Souza