Cleaning Out the Junk with Medical Bioremediation

B.E. Rittmann, K. Kemmish, J. Schloendorn, L. Jiang
Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, Tempe, AZ

Several major age-related diseases are associated with the long-term accumulation of pathogenic materials (i.e., "junk") within and between our bodies' cells: e.g., atherosclerosis (oxidized cholesterols in the artery wall), macular degeneration (fluorophores of the retinal pigment epithelial lipofuscin), and extracellular matrix dysfunction (advanced-glycation end-products in long-lived proteins). Medical bioremediation is a strategy to remove these accumulations from affected cells by using catabolic enzymes derived from environmental microorganisms. Medical bioremediation takes advantage of the nearly infinite metabolic diversity of environmental microorganism by adapting methods from environmental bioremediation and biocatalyst discovery. Our research addresses each of these areas, and we summarize recent results for cleaning out junk molecules associated with atherosclerosis and macular degeneration.

As a first step towards testing medical bioremediation, we isolated a range of bacterial species capable of degrading the pro-atherosclerotic model compound 7-ketocholesterol (7KC) and other pathogenic cholesterol derivatives found to accumulate in human atherosclerotic tissue. The fastest-degrading isolates were strains of Nocardia, and we identified key degradation intermediates for one Nocardia strain and proposed a 7KC-degradation pathway that is different from its cholesterol-degradation pathway. This raises the possibility that oxysterol-specific catabolic enzymes may be used for the selective elimination of pathogenic oxysterols from our arteries.

A2E, which accumulates in age-related macular degeneration, is a retinoid compound with strong a visual absorption spectrum. We failed to culture microbes on A2E for over two years. This led us to test the idea that some organisms may have enzymes to degrade A2E without necessarily being able to grow on it as the only carbon and energy source. Thus, we changed our strategy to testing microbial enzymes directly, without requiring growth on A2E as the only carbon and energy source. With our new strategy, we identified two enzymes able to degrade A2E: a peroxidase from horseradish and a cyanobacterial carotenoid cleavage dioxygenase.

Keywords: Medical bioremediation, Atherosclerosis, Macular degeneration