As much as we might want to pride ourselves on inventing drugs, nature invariably beat us to the punch. Before we got pain relief from aspirin, for example, its key ingredient salicin could be extracted by boiling willow bark. Before we stabilized heart problems with digitalin, we found its active glycosides in the foxglove flower. Before we attacked cancer with vincristine, this powerful alkaloid was identified in periwinkle plants on the island of Madagascar.

In fact, a huge portion of our pharmacopeia is taken directly from naturally occurring agents that act on specific biological targets of interest to us, such as interfering with receptors in infectious bacteria. Nor should that be surprising, says Nathan Magarvey, the Canada Research Chair in Chemical Biology and Natural Products at McMaster University. “Natural products have always had an advantage because they’re things that evolved in the cellular context,” Magarvey says. “They create an action regardless of whether they hit one or many targets.”

For Magarvey, the larger question is why some of these products generate significant biological actions while so many others do not. He and his colleagues are seeking the answer with an analytical tool that could set the stage for an entirely new perspective on how we go about looking for drugs. Magarvey’s group has developed an algorithm for extracting this information from the genomes of natural products. Dubbed Prediction Informatics for Secondary Metabolomes (PRISM), this modelling software draws on known reactions to predict the behaviour of peptides and polyketides extracted from these products. The result is a very fresh take on some very familiar chemistry. “Organisms that we had been working on in the lab for 30, 40 years — as soon as we had a genome, we got a totally different view,” Magarvey says. “That view led to us and others immediately finding molecules that we hadn’t seen before.”

Among the most venerable of these organisms was streptomyces, the bacterium that leapt to the forefront of modern medicine in the 1940s to become the source of our most powerful antibiotic compounds. Since then it has been picked over in countless pharmaceutical and academic laboratories. Now, PRISM has revealed a previously unknown dimension of this humble microbe. In a Nature Communications paper published this past February, Magarvey and others demonstrated how this computational resource can reveal previously unknown molecular scaffolds that are encoded in the streptomyces genome but not always expressed. According to Queen’s University chemistry professor David Zechel, who recently began working with Magarvey’s team, there is good reason to think that at least some of these variants will be pharmaceutically active. “If you think about it, that’s a brilliant strategy for evolving a response to a dynamic environment,” says Zechel. Bacteria were among the first living creatures to appear on Earth some 3.5 billion years ago and streptomyces has been around in its current form for at least 450 million years. They survived unthinkable planetary upheavals — including the creation of atmospheric oxygen via their own metabolism — by nurturing a wide-ranging genomic tool kit that would allow it to keep up with these changes. “These are the original combinatorial chemists,” Zechel says. With the help of such “chemists,” we may be able to find new drugs to help cope with problems like bacterial resistance to antibiotic compounds, adds Zechel. “We’ve only touched the tip of the iceberg. There’s actually another whole world of chemical space that we haven’t even explored yet.”