Beer That's Good for You

Nov. 6, 2008— -- Since headlines began trumpeting the antiaging effects of red wine a couple of years ago, the traditional toast to good health has become more meaningful. But students at Rice University, in Texas, think that beer drinkers shouldn't be left out. They're trying to engineer a yeast that produces the antiaging chemical found in red wine--resveratrol--and use it to brew "BioBeer" with a health boost.

"It's not going to prevent you from getting a beer gut from drinking too much beer, or from getting cirrhosis of the liver," says Taylor Stevenson, one of six undergraduates working on the project. "But people are already drinking beer, so why not make the activity a little healthier?"

Resveratrol was discovered in red wine in the 1990s, prompting scientists to wonder if it might explain the "French paradox"--the fact that the French have a relatively low death rate from heart disease, despite a diet relatively high in saturated fat. Resveratrol is now known to extend life span in various organisms, including fish, flies, and yeast, and aging mice fed high doses of the chemical are healthier in their old age. It's not known whether resveratrol has the same effects in humans.

The BioBeer project is an entry in the International Genetically Engineered Machine (iGEM) competition being held this weekend in Cambridge, MA. The event showcases student work in the field of synthetic biology, in which researchers string together blocks of DNA--whether artificial or naturally occurring--in order to build useful new organisms from scratch.

Many of the blocks of DNA identified by synthetic-biology researchers have been recorded in the open-source Registry of Standard Biological Parts at MIT. Participants in the iGEM competition submit their own DNA blocks to the registry, and they may use parts from the registry in their projects. The BioBeer team will submit 16 blocks to the registry, Stevenson says.

Other researchers have engineered yeast to produce resveratrol under aerobic conditions, but that's of limited use, since resveratrol is deactivated by exposure to oxygen. The Rice students are trying to create a yeast that produces the chemical during fermentation. They say that the method could be used to introduce other air-sensitive pharmaceuticals into beer, which is the most popular alcoholic beverage in the United States.

"I think of it as a drinkable bioreactor," says Thomas Segall-Shapiro of the BioBeer team. "It's completely ready to go once it's brewed."

The BioBeer team has equipped yeast with two genes that code for enzymes required for resveratrol production.

The first enzyme converts the amino acid tyrosine into coumaric acid, and the second turns that into resveratrol.

Resveratrol is found in low levels in hops, the raw ingredient of beer. "We're just trying to enhance something that's probably there at very low levels," says Jonathan Silberg, faculty advisor for the BioBeer project at Rice. "We're not trying to undermine wine's little niche in any way. It's a different market."

"I'm sure there would be people interested in drinking resveratrol in beer rather than wine," says Rafael de Cabo of the National Institute on Aging, who has studied the effects of resveratrol. But "you can add resveratrol directly to the beer," he says. "You don't need to make a yeast that will make resveratrol."

Stevenson, though, says that because resveratrol is sensitive to air and light, the process of extracting it from plants and then purifying it may impair its effectiveness. "Beer's actually this really ideal transport vessel for these light and air-sensitive pharmacological products," he says.

The idea of brewing resveratrol beer is "potentially good," says Leonard Guarente, a professor at MIT who's studied the effects of resveratrol, but the BioBeer team must prove that it's bioactive.

The students plan to test their BioBeer on fruit flies to confirm that it extends their life spans. Researchers have shown that resveratrol gives flies, mice, and worms longer, healthier lives, mimicking the effects of a very low-calorie diet. Resveratrol is also being tested as a treatment for type 2 diabetes.

Resveratrol is found in modest amounts in peanuts and some berries, including cranberries and blueberries, but it is more plentiful in the skins of grapes. When grapes are fermented to produce red wine, the skins are left on, but they're removed earlier in the process of producing white wine--hence the greater resveratrol concentration in red wine.

The Rice University team has engineered yeasts to produce resveratrol, and they're about to brew their first batch of BioBeer.

Resveratrol shouldn't affect the taste of the beer, Silberg says, but another biological product of the yeast might. One of the enzymes that the students added to the yeast not only catalyzes the first step in the production of resveratrol but also transforms phenylalanine into cinnamic acid. Cinnamic acid has a honeyed, floral taste, which "sounds like a plus for flavor," Stevenson says. Like five of the six team members, though, Stevenson isn't old enough to legally sample his BioBeer.

Mark Leid, a professor in the Department of Pharmaceutical Sciences at Oregon State University, wonders whether the BioBeer will contain enough resveratrol to have health benefits when consumed in moderate amounts. That remains to be seen, Stevenson says, but he adds that the bioengineered yeast could be further modified to optimize resveratrol production.

"The amount in red wine's actually not that much compared to what might be possible with this process," Segall-Shapiro says.

At the moment, Stevenson says, the yeast does not contain a gene that actively exports resveratrol out of the cell. Some will diffuse out of the cell on its own, but in the short term, he says, the beers that impart the greatest health benefits could be unfiltered brews like Hefeweizens, which are clouded by yeast that drinkers swallow whole. Although plenty of people already pop resveratrol pills, "there are a lot of things that need to be done before we put resveratrol in foods or we put it in a pill," de Cabo says. "There are a number of things we don't know about resveratrol."

Besides, he says, "we're running on hope that some of the things we've seen in the mouse studies will replicate in humans."