Medical bioremediation: a concept moving toward reality.
Abstract A major driver of aging is catabolic insufficiency, the inability of our bodies to break down certain substances that accumulate slowly throughout the life span. Even though substance buildup is harmless while we are young, by old age the accumulations can reach a toxic threshold and cause disease. This includes some of the most prevalent diseases in old age-atherosclerosis and macular degeneration. Atherosclerosis is associated with the buildup of cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the artery wall. Age-related macular degeneration is associated with carotenoid lipofuscin, primarily the pyridinium bisretinoid A2E. Medical bioremediation is the concept of reversing the substance accumulations by using enzymes from foreign species to break down the substances into forms that relieve the disease-related effect. We report on an enzyme discovery project to survey the availability of microorganisms and enzymes with these abilities. We found that such microorganisms and enzymes exist. We identified numerous bacteria having the ability to transform cholesterol and 7-ketocholesterol. Most of these species initiate the breakdown by same reaction mechanism as cholesterol oxidase, and we have used this enzyme directly to reduce the toxicity of 7-ketocholesterol, the major toxic oxysterol, to cultured human cells. We also discovered that soil fungi, plants, and some bacteria possess peroxidase and carotenoid cleavage oxygenase enzymes that effectively destroy with varied degrees of efficiency and selectivity the carotenoid lipofuscin found in macular degeneration.
Schloendorn
John
J
Biodesign Institute at Arizona State University, Tempe, Arizona, USA. zauberkugel@gmail.com
Webb
Tim
T
Kemmish
Kent
K
Hamalainen
Mark
M
Jackemeyer
David
D
Jiang
Lijing
L
Mathieu
Jacques
J
Rebo
Justin
J
Sankman
Jonathan
J
Sherman
Lindsey
L
Tontson
Lauri
L
Qureshi
Ateef
A
Alvarez
Pedro
P
Rittmann
Bruce
B
D001711:Biotransformation / Q000187:drug effects; D002338:Carotenoids / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002789:Cholesterol Oxidase / Q000378:metabolism; D002853:Chromatography, Liquid; D004783:Environmental Microbiology; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007553:Isotope Labeling; D007653:Ketocholesterols / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D010105:Oxygenases / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D011726:Pyridinium Compounds / Q000737:chemistry / Q000378:metabolism; D012176:Retinoids / Q000737:chemistry / Q000378:metabolism; D013261:Sterols / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
C112040:A2-E (N-retinylidene-N-retinylethanolamine); D004952:Esters; D007653:Ketocholesterols; D011726:Pyridinium Compounds; D012176:Retinoids; D013261:Sterols; D002338:Carotenoids; D002789:Cholesterol Oxidase; D010544:Peroxidases; D010105:Oxygenases; C003001:7-ketocholesterol