title: Medical bioremediation: a concept moving toward reality.
abstract: 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.
authors.affiliation: Biodesign Institute at Arizona State University, Tempe, Arizona, USA. zauberkugel@gmail.com
authors.forename: John
authors.initials: J
authors.lastname: Schloendorn
authors.forename: Tim
authors.initials: T
authors.lastname: Webb
authors.forename: Kent
authors.initials: K
authors.lastname: Kemmish
authors.forename: Mark
authors.initials: M
authors.lastname: Hamalainen
authors.forename: David
authors.initials: D
authors.lastname: Jackemeyer
authors.forename: Lijing
authors.initials: L
authors.lastname: Jiang
authors.forename: Jacques
authors.initials: J
authors.lastname: Mathieu
authors.forename: Justin
authors.initials: J
authors.lastname: Rebo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sankman
authors.forename: Lindsey
authors.initials: L
authors.lastname: Sherman
authors.forename: Lauri
authors.initials: L
authors.lastname: Tontson
authors.forename: Ateef
authors.initials: A
authors.lastname: Qureshi
authors.forename: Pedro
authors.initials: P
authors.lastname: Alvarez
authors.forename: Bruce
authors.initials: B
authors.lastname: Rittmann
mesh_terms: 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
chemical_list: 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