New drug candidates identified in bacteria

It is mainly known about cyanobacteria that they carry out photosynthesis like plants. However, this group of bacteria also produces many interesting natural products, including the newly discovered lipopeptides. (Photograph: Adobe Stock)

Bacteria show great promise as a source of active ingredients. Using computer-​based genome analysis, researchers at ETH Zurich have now discovered a new class of natural products that might one day serve as antibiotics.

Animals, plants, fungi and bacteria – each and every organism carries a whole armoury of chemical compounds that enable it to interact with its environment, attract partners or deter enemies. Bacteria, among the oldest forms of life on earth, contain a host of complex chemical structures, accumulated over millions of years of evolution.

Many of these metabolites have proved highly effective as active ingredients in human medicine. Indeed, around one-​third of the medicinal drugs approved today are derived from natural products. This includes most antibiotics.

Unlocking the chemical mysteries of bacteria is, however, not all that easy. The snag is that many types of bacteria are difficult, if not impossible, to cultivate in the laboratory. And, frequently, it is only in tandem with other organisms that they produce natural products that are of interest to medicine.

The application of bioinformatics and modern DNA sequencing methods can significantly expedite the hunt for new active ingredients. Using this approach, a research team led by Jörn Piel, Professor of Microbial Interactions at ETH Zurich, has now discovered a new synthetic pathway for peptide natural products that appears to be widespread in bacteria.

The present study describes a total of three enzymes that attach fatty acids of differing chain lengths to a peptide. “Initial experiments show that it is indeed possible to produce these customised lipopeptides in the lab,” says Anna Vagstad, another of the study’s lead authors. The next step will be to investigate the biological activity of this new substance class.

“There’s often minimal financial incentive for pharmaceutical companies to develop new antibiotics,” Vagstad says, “but we researchers can at least take the first step, which is to search for new active ingredients.”

Silvie Cuperus