Rare soil microbe, a new antibiotic candidate for drug-resistant infections

Scientists have identified a potential candidate for antibiotic drug development in a soil bacterium called Lentzea flavaviverrucosa

Demand for new antibiotics is surging as drug resistance and emerging infections become a growing global health threat

Scientists at Washington University in St.

"Rare actinomycetes are an underexplored source of new bioactive compounds," said Joshua Blodgett, assistant professor of biology in Arts and Sciences and co-corresponding author of the new study

Joshua Blodgett, assistant professor of biology at Washington University in St.

Bioactive components produced by actinomycetes form the basis of many clinically useful drugs, especially antibiotics and anticancer drugs

But some of these microbes -- known as rare actinomycetes -- have been catalogued, but so far haven't been extensively studied

The definition of "rare" isn't set in stone, but these actinomycetes tend to be harder to find in nature than other fungi, and they may grow more slowly, Blodgett said

Among the rare actinomycetes, Lentzea flavaviverrucosa stood out, Blodgett said

"It has unusual biological properties, encoding unusual enzymatic properties that drive unexpected chemical reactions, all hidden within a largely overlooked bacterial population,

Blodgett and his collaborators, including co-corresponding author Shugeng Cao of the University of Hawaii, found that molecules produced by this rare actinomycete are active against certain types of human ovarian cancer, fibrosarcoma, prostate cancer and leukemia cell lines

Scientists first discovered Lentzea flavaviverrucosa while searching for rare actinomycetes whose genetic signature suggested they could make piperazine molecules

But as the researchers dug deeper, they found some other surprises

"At a high level, it seems like one region of the genome might produce two different molecules

Early clues proved accurate
.
Using a combination of modern metabolomics and chemical and structural biology techniques, Blodgett and his team were able to show that this rare actinomycete actually gave rise to two distinct organisms from a set of genes known as superclusters.
active molecules
.

Superclusters are rare in biology
.
This particular Superclusters encoded two distinct molecules that were later welded together in an atypical chemical reaction
.

"Nature welds two different things together," Blodgett said
.
"It turns out that against several different cancer cell lines, when you combine A and B, it becomes something more effective
.
"

Reference: “Discovery of unusual dimeric piperazyl cyclopeptides encoded by a DSM 44664 biosynthetic supercluster” 11 April 2022, Proceedings of the National Academy of Sciences .

DOI: 10.
1073/pnas.
2117941119