Bioprospectors mine microbial genomes for antibiotic gold

Summary

In brief The discovery of penicillin nearly 100 years ago started a gold rush to find new antimicrobials. Scientists mined microscopic bacteria and fungi for compounds that could help fight off infection. But over time the rate of antimicrobial discoveries slowed to a crawl. Now, modern-day bioprospectors are using genomics, synthetic biology, and AI to dig deeper than they ever have before. A new golden age of antibiotics may be upon us, say some on the hunt, though getting a drug candidate into the clinic isn’t so easy. In March, the journal Nature published the discoveries of two paradigm-breaking antimicrobial compounds in as many weeks: a polyene macrolide antifungal called mandimycin and a lasso peptide antibiotic called lariocidin. Both these compounds, which use never-before-seen antimicrobial mechanisms, were found using techniques that let researchers look deep into the chemical diversity of microbes—much deeper than a typical antibiotic or antifungal screen might go. And it’s not just these two molecules. Scientists are using the new approaches to discover countless other antimicrobial compounds with the potential to become drugs. Gerry Wright, a biochemist at McMaster University who led the research group that discovered lariocidin, likens the hunt for antimicrobials to the gold mining operations in his native Ontario, Canada. “In the old days, you’d look for a gold vein and you’d blast out that slag to get as much gold as you could,” he says. “Now, coming back with different tools, you can remine that slag and get more gold or maybe other precious metals.” The first gold rush The first bioprospecting operations took place nearly 100 years ago. The antibiotic penicillin was famously discovered in 1928 by Alexander Fleming, who isolated the compound from a fungus that was contaminating his bacterial cultures. That marked the start of the first “golden age of natural product antibiotic discovery,” according to a frequently cited review paper (Curr. Opin. M...