Team:Rice University

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Revision as of 23:30, 27 October 2008

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!

BioBeer: Producing Resveratrol During Beer Fermentation

trans-Resveratrol

Resveratrol

• First identified as the active component in C. quinquangulata (cinnamon) extract responsible for anti-inflammatory properties.
  
• Normally used as a defense mechanism in plants in response to fungal pathogens and UV irradiation.
  
• Main source in human diet is red wine, but significant amounts are also found in grape juice, peanuts, cranberry juice, and other sources.
• There is a tremendous interest in the potential of resveratrol for various health benefits. A PubMed search for 'resveratrol' returns 2,470 scientific articles.

Resveratrol and Yeast

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.

• 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.
• "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."

Resveratrol has been shown to provide a wealth of health benefits.

Health Benefits

• 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]
• 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]
• Upregulates the antioxidant systems of cells, such as SuperOxide Dismutase and glutathione, and these cells are protected against oxidative damage [16,17].
• Resveratrol decreases several modes of inflammation [18-21].
• 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].
• 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].
• 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].

Why resveratrol in beer?
-Beer made up 85.8% of all alcoholic beverage consumption (in total volume) in 2005.
-->Annual per capita consumption of Beer (2005) = ~20 gallons
-->Annual per capita consumption of Wine (2005) = ~2.5 gallons

-If resveratrol can be produced during fermentation, it provides an additional health benefit at no additional cost.
-->The resveratrol is produced in a ready-to-consume format!
-->Dark and anaerobic conditions required for fermentation improve resveratrol stability.

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