Engineering away lysosomal junk: medical bioremediation.
Atherosclerosis, macular degeneration, and neurodegenerative diseases such as Alzheimer's disease, are associated with the intracellular accumulation of substances that impair cellular function and viability. Reversing this accumulation may be a valuable therapy, but the accumulating substances resist normal cellular catabolism. On the other hand, these substances are naturally degraded in the soil and water by microorganisms. Thus, we propose the concept of "medical bioremediation," which derives from the successful field of in situ environmental bioremediation of petroleum hydrocarbons. In environmental bioremediation, communities of microorganisms mineralize hydrophobic organics using a series of enzymes. In medical bioremediation, we hope to utilize one or several microbial enzymes to degrade the intracellular accumulators enough that they can be cleared from the affected cells. Here, we present preliminary, but promising results for the bacterial biodegradation of 7-ketocholesterol, the main accumulator of foam cells associated with atherosclerosis. In particular, we report on the isolation of several Nocardia strains able to biodegrade 7-ketocholesterol and as an ester of 7-ketocholoesterol. We also outline key intermediates in the biodegradation pathway, a key step towards identifying the key enzymes that may lead to a therapy.
Rittmann
Bruce E
BE
Center for Environmental Biotechnology, Biodesign Institute, Arizona State University, Tempe, Arizona 85287-5701, USA. Rittmann@asu.edu
Schloendorn
John
J
D050197:Atherosclerosis / Q000378:metabolism; D001673:Biodegradation, Environmental; D005487:Foam Cells / Q000378:metabolism; D005818:Genetic Engineering; D006838:Hydrocarbons / Q000737:chemistry; D007653:Ketocholesterols / Q000737:chemistry* / Q000378:metabolism; D019787:Linoleic Acid / Q000737:chemistry*; D008136:Longevity; D008247:Lysosomes / Q000378:metabolism*; D008660:Metabolism; D008956:Models, Chemical; D009615:Nocardia / Q000378:metabolism*; D010578:Petroleum / Q000378:metabolism
D006838:Hydrocarbons; D007653:Ketocholesterols; D010578:Petroleum; D019787:Linoleic Acid; C003001:7-ketocholesterol