A CRISPR approach to greener beer

By Jenna Gallegos

January 22, 2019

First came the IPAs and then the double IPAs, triple IPAs, and imperial IPAs. The theme? More hops. Like most hipsters, I love a good hoppy beer. So I was disappointed to learn that hops are not environmentally friendly. Fortunately, scientists are brewing up new ways to decrease the environmental footprint of a pint, though ideologies could prevent these green beers from ever making it to tap houses.

Dr. Jay Keasling is a renowned synthetic biologist with a passion for all things green. I’ve previously written about the many ways synthetic biology can help save the environment, so I anxiously anticipated his keynote talk at one of the biggest synthetic biology conferences of the year. What I didn’t expect is that, nestled in between presentations about novel diagnostics, biofuels and gene therapy, Keasling talked about beer.

Beer is made mainly from wheat, barley and hops. Along with the massive amounts of water and energy used in the brewing process, growing these crops has a substantial environmental footprint.  Hops grown on US soils alone guzzle a staggering 26 billion gallons of water every year. That works out to about 50 pints of water per beer, not to mention the carbon costs of transporting the hops. In addition to the environmental impact, hops pose a significant challenge to brewers.

Hops are covered in tiny hair-like appendages called trichomes — the same structures responsible for THC in the closely related marijuana plant. These trichomes produce oils that are full of the bitter flavor compounds called terpenes that we know and love in beer. Like vintages of wine, hops grown in slightly different environments produce varied combinations of terpenes, which makes brewing a consistent-tasting hoppy beer challenging.

But the floral flavor behind the very popular Cascade hops comes mainly from two terpenes: linalool and geraniol. Researchers in Keasling’s lab at the University of California at Berkeley set out to engineer the genetic pathways that produce linalool and geraniol into brewers yeast.

To make both compounds in the right ratios without inhibiting fermentation, they had to test dozens of combinations of genetic parts. They modeled these combinations virtually and then tested them in the yeast. Ultimately, they used CRISPR to introduce genes from mint and basil and tweak a few of the yeast’s own genes.

The resulting yeast were used to brew beer that was compared to dry-hopped brews in a taste test at Lagunitas brewery. In dry hopping, hops are added to the beer after fermentation, resulting in a hoppy aroma without a bitter taste. A panel of tasters identified more hoppy flavor and aroma in the beer brewed with genetically engineered yeast than beer that had been dry hopped.  Importantly, the level of linalool and gernaiol was also more consistent than in conventionally hopped beer.

When Keasling presented this work at the American Institute of Chemical Engineer’s annual Synthetic Biology: Engineering, Evolution, and Design meeting, an audience member asked if the resulting beer would be considered genetically modified. Keasling explained that beer brewed with genetically engineered yeast does not invoke GMO labels or regulations, but beer brewed with regular yeast using sugar from genetically engineered plants does.

I’ve written about this paradox before, and was reminded of another presentation I heard about genetic engineering and beer a few years before. Peggy Lemaux’s lab, also at Cal Berkeley, had used genetic engineering to tackle a different challenge in the brewing industry: malting.

During malting, complex branched chains of starches in barley are broken down into simpler sugars. These sugars feed the yeast while they’re fermenting the grain into alcohol. Lemaux and colleagues discovered that, by adding a gene for one of the “starch debranching” enzymes from wheat to barley, they could decrease the malting process from three to five days to as few as one to two days.

Although this work was completed in the early 2000s, the fast-malting barley never made it into commercial brews. The funders backing the project worried that nobody would want to drink beer brewed with genetically modified barley.

If the hop-free hoppy beer made possible by the work in Keasling’s lab makes it to shelves, it is unclear whether it will sport a label distinguishing its unique history.  That decision will likely be left up to the brewers. And while cheese makers have relied on genetically engineered organisms since the ’80s, brewers and vintners have been more hesitant.  It seems they’re worried consumers won’t bite. People are ironically skeptical when it comes to their choice of booze, despite their acceptance of a much less benign ingredient — alcohol.