New Antibiotic Candidate Identified in Soil Bacterium


Actinomycetes produce bioactive components that form the basis for many clinically useful drugs, especially antibiotics and anticancer agents.

Since the 1940s, pharmaceutical companies have analyzed many common actinomycetes to see what they might produce.

Today, about two-thirds of all antibiotics used in hospitals and clinics are derived in part from actinomycetes.

But some of these microbes — known as the rare actinomycetes — have been catalogued but not extensively studied so far.

“These actinomycetes tend to be more difficult to find in nature than others, and they may grow more slowly,” said lead author Dr. Joshua Blodgett, a researcher in the Department of Biology at Washington University in St. Louis.

For these and other reasons, many rare actinomycetes have not been fully characterized for drug discovery and biotechnology purposes.

Among the rare actinomycetes, Lentzea flaviverrucosa emerged as a standout.

“It has unusual biology, encoding for unusual enzymology, driving the production of unexpected chemistry, all harbored within a largely overlooked group of bacteria,” Dr. Blodgett said.

The researchers discovered that this rare actinomycete produces molecules that are active against certain types of human ovarian cancer, fibrosarcoma, prostate cancer and leukemia cell lines.

They initially spotted Lentzea flaviverrucosa when they went looking for rare actinomycetes with a genetic hallmark that indicates that they can make piperazyl molecules.

These molecules incorporate an unusual building block that is a flag for potential drug-like activities.

But as the researchers dug deeper, they uncovered a few other surprises.

“At a high level, it looked as if one region of the genome might be able to make two different molecules. That’s just a little strange,” Dr. Blodgett said.

“Usually we think of a gene cluster, groups of genes that are like blueprints for making individual drug-like molecules.”

“But it looked like there was almost too much chemistry predicted within this single cluster.”

Using a combination of modern metabolomics with chemical and structural biology techniques, the authors were able to show that this rare actinomycete actually produces two different bioactive molecules from a single set of genes called a supercluster.

This particular kind of supercluster encodes for two different molecules that are later welded together in an atypical chemical reaction.

“Nature is welding two different things together. And, as it turns out, against several different cancer cell lines, when you stick A and B together, it turns into something more potent,” Dr. Blodgett said.

A paper on the findings will be published in the Proceedings of the National Academy of Sciences.