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| | + | [[Team:Rice_University/OUR TEAM|OUR TEAM]] ::: [[Team:Rice_University|SUMMARY]] ::: [[Team:Rice_University/BACKGROUND|BACKGROUND]] ::: |
| | + | [[Team:Rice_University/STRATEGY|STRATEGY]] ::: [[Team:Rice_University/CONSTRUCTS|CONSTRUCTS]] ::: [[Team:Rice_University/RESULTS|RESULTS]] ::: [[Team:Rice_University/CONCLUSIONS|ONGOING WORK]] |
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| - | <!--- The Mission, Experiments --->
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| - | == '''Welcome to Rice University's 2008 iGEM wiki page.''' == | + | |
| - | Our project for this year is BIOBEER, where we are genetically engineering the biosynthetic pathway for resveratrol production into a brewing yeast strain. Resveratrol has been shown to have a plethora of health benefits, including anti-cancer and anti-viral activity, cardio- and neuro-protective effects, modulation of diabetes, and anti-aging effects. Although research has been done previously to produce resveratrol in various organisms, no one to date has developed a yeast strain able to synthesize resveratrol in a de novo manner. We are going one step further, characterizing resveratrol production during anaerobic fermentation with the intent of creating a beer that contains all the health benefits of wine. Get ready for resveratrol in a fizzy ready-to-consume beverage!
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| - | == '''BioBeer: Producing Resveratrol During Beer Fermentation''' == | + | {|align="justify" style="background-color:#FFFFFF;text-indent: 15pt;text-align:justify" cellpadding="30" width="90%" |
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| | + | Resveratrol, a phytochemical in plants, has been implicated as a natural product that extends lifespan and prevents cancer, coronary disease and neurodegenerative maladies. Unfortunately, resveratrol is only present at appreciable levels in a small number of foods, such as red wine, peanuts, and blueberries. To create an alternative source for resveratrol consumption, we are introducing a biosynthetic pathway for this compound into a brewing strain of yeast and examining whether this strain can be engineered to produce resveratrol during beer fermentation. Given the high worldwide consumption of beer and the low cost of production, unfiltered beer brewed using our genetically modified yeast should provide a cost-effective source of pharmacologically-active resveratrol. This engineering approach should be useful for cheap biosynthesis of other oxygen-sensitive prophylactics. |
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| - | [[Image:trans-resveratrol.jpg|right|frame|none|trans-Resveratrol]]
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| - | === '''Resveratrol''' ===
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| - | :* First identified as the active component in ''C. quinquangulata'' (cinnamon) extract responsible for anti-inflammatory properties. <BR>
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| - | :* Normally used as a defense mechanism in plants in response to fungal pathogens and UV irradiation. <BR>
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| - | :* Main source in human diet is red wine, but significant amounts are also found in grape juice, peanuts, cranberry juice, and other sources.
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| - | :* There is a tremendous interest in the potential of resveratrol for various health benefits. A PubMed search for 'resveratrol' returns '''2,470''' scientific articles.
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| - | ==='''Resveratrol and Yeast''' ===
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| - | [[Image:RSVYeast.jpg|left|thumb|200px|Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.]]
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| - | :* Resveratrol has been extensively investigated in the Saccharomyces cerevesiae model system. In August 2003, Sinclair and Scherer reported 70% increase in yeast lifespan after induction with 10uM resveratrol.
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| - | :*"In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2, a member of the conserved sirtuin family of NAD+-dependent protein deacetylases2, 3, 4, 5, 6. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan7, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor. the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating SIRT1-dependent deacetylation of p53."
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| - | [[Image:RSV-health.jpg|left|thumb|300px|Resveratrol has been shown to provide a wealth of health benefits.]]
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| - | === '''Health Benefits''' ===
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| - | :* '''Improved cardiovascular function''': resveratrol has been shown to have cardioprotective effects such as the suppression of atherosclerosis, inhibition of platelet aggregation, vasorelaxation promotion, and modulation of triglyceride blood levels, in a wide variety of in vitro and in vivo models. [1-4]
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| - | :* '''Inhibition of carcinogenesis''': one well-documented effect of resveratrol is the ability to induce cell death specifically in cancerous cells. This property of resveratrol has been shown for a wide variety of cancers, including colon cancer [5-7], pancreatic cancer [8], prostate cancer [9,10], breast cancer [11,12], and skin cancer [13,14]. In fact, several phase I human clinical trials are investigating the administration of resveratrol as a cancer therapy [15,16]
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| - | :* '''Upregulates the antioxidant systems of cells''', such as SuperOxide Dismutase and glutathione, and these cells are protected against oxidative damage [16,17].
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| - | :* '''Resveratrol decreases several modes of inflammation''' [18-21].
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| - | :* '''Maintenance of neural pathways''': mouse models of Alzheimers and Parkinsons demonstrate the potential of resveratrol as a neuroprotective agent in degenerative neural diseases [22,23]. Experiments with rats, mice, and gerbils show that resveratrol administration protects against brain damage following ischemic stroke [24-26].
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| - | :* '''Improves insulin sensitivity''': resveratrol has been shown as a potent therapeutic for type 2 diabetes [27]. Pharmaceuticals based on resveratrol-like compounds for the treatment of diabetes are currently in Phase I clinical trials [28].
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| - | :* '''Mimics caloric restriction''' in mammals and is '''proven to extend lifespans''' in invertebrates [29,30], a fish model [31] and is shown to reduce the genetic changes associated with aging in a mammalian mouse model [4,32].
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| - | [[Image:brewing.jpg|left]]
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| - | Why resveratrol in beer? <BR>
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| - | -Beer made up 85.8% of all alcoholic beverage consumption (in total volume) in 2005. <BR>
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| - | -->Annual per capita consumption of Beer (2005) = ~20 gallons <BR>
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| - | -->Annual per capita consumption of Wine (2005) = ~2.5 gallons <BR>
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| - | -If resveratrol can be produced during fermentation, it provides an additional health benefit at no additional cost. <BR>
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| - | -->The resveratrol is produced in a ready-to-consume format! <BR>
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| - | -->Dark and anaerobic conditions required for fermentation improve resveratrol stability.
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| - | The Rice 2008 Synthetic BiOWLogists
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| - | [[Image:iGEM-2008-Splash.jpg|400px|right]]
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| - | {| style="color:#1b2c8a;background-color:#0c6;" cellpadding="3" cellspacing="1" border="1" bordercolor="#fff" width="62%" align="center"
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| - | !align="center"|[[Team:Rice_University|Home]]
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| - | !align="center"|[[Team:Rice_University/Team|The Team]]
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| - | !align="center"|[[Team:Rice_University/Project|The Project]]
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| - | !align="center"|[[Team:Rice_University/Parts|Parts Submitted to the Registry]]
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| - | !align="center"|[[Team:Rice_University/Notebook|Notebook]]
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