Bioactive Secondary Metabolites from Acid Mine Waste Extremophiles

摘要

The extremophilic microbes of the Berkeley Pit Lake are a valuable source of new and interesting secondary metabolites. It is of particular interest that these acidophilic microbes produce small molecule inhibitors of pathways associated with >low pH and >high Eh. These same small molecules also inhibit molecular pathways induced by reactive oxygen species (ROS) and inflammation in mammalian cells. Low pH is a hallmark of inflammation and high Eh is one of ROS, so the suitability of this collection as a source of bioactive metabolites is actually quite biorational. Compound isolation was guided by inhibition of caspase-1 and matrix metalloproteinase-3, and active compounds were sent to the National Cancer Institute-Developmental Therapeutics Program and Memorial Sloan Kettering Cancer center for evaluation as either antiproliferative or cytotoxic agents.