Despite their ecologic similarity, soils from three
geographically distinct areas of the American southwest harbor vastly different
collections of small, biosynthetic genes, a finding that suggests the existence
of a far greater diversity of potentially useful products than was previously
supposed. The research is published in the May issue of Applied and Environmental Microbiology.
Natural compounds have been the sources of the majority of
new drugs approved by the US Food and Drug Administration, and bacteria have
been the biggest single source of these therapeutically relevant compounds.
Most bacterially-derived antibiotic and anticancer agents were discovered by
culturing bacteria from environmental samples, and then examining the
metabolites they produce in laboratory fermentation studies. But the vast
majority of bacterial species cannot be cultured, which suggested that the
world might be awash in potentially useful, but unknown bacterial metabolites.
In this study, Sean Brady of the Howard Hughes Medical
Institute, Rockefeller University, New York, NY, and colleagues extracted DNA
from soils from the Sonoran Desert of Arizona, the Anza Borrego section of the
Sonoran Desert of California, and the Great Basin Desert of Utah. They used
this DNA to construct very large metagenomic DNA libraries, and screened these
libraries for three of the most common classes of small molecule biosynthesis
systems, type I modular polyketides, type II iterative polyketides, and
non-ribosomal peptides, says Brady.
The investigators used PCR to amplify collections of gene
fragments from each of the three libraries and compared these to assess the
similarities and differences between the collections of genes cloned from each
environment, says Brady.
“Our work suggests that the genomes of environmental
bacteria could encode many additional drug-like molecules, including compounds
that might serve, among other things, as new antibiotics and anticancer
agents,” says Brady. “This is a small preliminary study that warrants
additional investigations of more environments and more extensive sequence
analysis, but it suggests that environmental bacteria have the potential to
encode a large additional treasure trove of new medicines.”
Download a copy of the article
(B.V.B. Reddy, D. Kallifidas, J.H. Kim, Z. Charlop-powers,
Z. Feng, and S.F. Brady, 2012. Natural product biosynthetic gene diversity in
geographically distinct soil microbiomes. Appl. Environ. Microbiol.
78:3744-3752.)
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