Microbe Magazine

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About 200 miles from Yellowstone National Park, is a site not as scenic, yet proving nearly as exotic in terms of its rich diversity of extremophiles. Instead of geysers and hot springs, the Berkeley Pit in Butte, Mont., contains 30 billion gallons of highly acidic waters (pH 2.5) from abandoned copper mines. The Berkeley Pit is the largest site in the Environmental Protection Agency’s Superfund program, which provides money for environmental cleanup at hazardous waste sites. Although nearly saturated with sulfates of iron, copper, aluminum, and zinc, the seemingly inhospitable waters and sediments in the Berkeley Pit yield more than 60 different microorganisms, including some that produce compounds that kill cancer cells and are active against other drug discovery targets, according to Andrea and Donald Stierle at Montana Tech of the University of Montana in Butte and their collaborators.

More than a decade ago, Andrea Stierle identified Euglena as the main component of a green slime growing on a piece of wood that had been submerged in the Berkeley Pit. “It was the first time we realized something could grow there,” she says. Since then, the Stierles and their collaborators turned that casual encounter with slime on a stick into a more-systematic analysis of the microbial contents within the pit ecosystem. They also are selectively analyzing the biosynthetic capacities of some of those microbes.

Among the pit fungi is a Penicillium species that produces a particularly potent, novel spiroketal compound that tests positive in signal transduction enzyme inhibition assays for matrix metalloproteinase-3 (MMP-3) and caspase-1, according to the Montana Tech team. When screened against 60 human cancer cell lines, nanomolar amounts of this compound, called berkelic acid, inhibit the ovarian cancer line OVCAR-3, according to collaborators at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) in Bethesda, Md. Detailed findings appear in the July 7, 2006 issue of the Journal of Organic Chemistry.

The team earlier isolated and characterized two novel polyketide-terpenoid metabolites, called berkeleydione and berkeleytrione, from another Penicillium species found in the Berkeley Pit. Micromolar amounts of these two compounds also inhibit MMP-3 and caspase-1, and berkeleytrione shows selective activity against non-small-cell lung cancer in similar NCI screening tests. These results are described in detail in the March 18, 2004, issue of Organic Letters.

In addition to fungi, the Stierles also collected bacteria, algae, and protozoa from the Berkeley Pit. “Every ecosystem, no matter how harsh, harbors diverse and rich populations of previously undiscovered microbes,” she says, noting that the metal-rich environment of the Berkeley Pit resembles natural volcanic-acid lakes as well as other mine-associated lagoons. “It would be worthwhile to look at these similar ecosystems for unusual microbes.”

“The potential is huge that this could be another Yellowstone,” says Tim Ford, head of microbiology at Montana State University in Bozeman. One problem, which he suggests is short-sighted, is that proposals to study the microbes of Yellowstone tend to prove more attractive to reviewers than do proposals focusing on those of the Berkeley Pit. “Any microorganisms that live in that environment have got to have unique metabolic pathways in order to survive,” he says, noting that their enzymes or metabolites could prove useful in biotechnology, pharmacology, or remediation.