Researchers have not yet found a way to turn dirt into gold, but they are
trying to find something valuable in it nonetheless: starting materials for
novel pharmaceuticals. As reported in the journal Angewandte
Chemie, a research team headed by Sean F. Brady at the Rockefeller University
in New York has now isolated DNA from "dirt" (samples of desert soil
from Utah) that encodes enzymes for a new biosynthetic pathway to make polyketides.
After introducing this DNA into Streptomyces albus, this bacteria produced a
previously unknown natural product named erdacin, which is a highly active antioxidant.
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We owe a number of our modern drugs to microorganisms, especially various
antibiotics. Every habitat contains countless previously unknown microbes. One
approach to the search for new drugs is thus the cultivation of such microbes
in the laboratory. Extracts of their cultures can then be tested for biological
activity. However, the majority of these microorganisms cannot be cultivated
under current laboratory conditions. It has previously been shown that cultivation
is not necessarily required in order to gain access to the natural products
microbes produce: DNA can be extracted directly from environmental samples,
such as a handful of soil, and stored in “environmental DNA libraries”.
It is a particular challenge to extract complete groups of genes that belong
together, known as gene clusters, from such libraries. Brady’s team has
now been able to isolate genes that encode enzymes for a special biosynthetic
pathway (Type II polyketide synthase pathway) from a library of DNA extracted
from desert soil. The researchers incorporated the genes from the desert soil
into the bacterium Streptomyces albus, which then produced a novel polyketide.
Polyketides are a group of natural products; their common trait is their biosynthesis
by way of polyketide precursors. Their chemical structures and biological properties
vary widely. Polyketides include many important drugs, including tetracycline
and the antibiotic erythromycin.
The new polyketide, produced by the gene cluster isolated from soil, was named
erdacin, which is derived from the Anglo-Saxon word “erda” for soil.
By using NMR spectroscopy and X-ray structural analysis, they were able to determine
its structure: a pentacyclic ring system made of one five-membered and four
six-membered rings that are linked in a previously unknown manner. Erdacin is
a strong antioxidant that is twice as active as well-known antioxidants such
as vitamin C.
Posted August 3rd, 2009
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