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Genome Editing Yields Quality Beer Without Hops

Hops flowers

Hops flowers (ulleo, Pixabay)

21 March 2018. Academic scientists studying synthetic biology with help from professional brewers used genome editing to engineer yeast that produces beer with the taste of hops, but without adding hops. The team from University of California in Berkeley, led by a former postdoctoral researcher who started a brewery science company, describe their process and blind taste tests in yesterday’s issue of the journal Nature Communications.

Flowers from hops plants provide a characteristic bitterness and flavor for beer, particularly in popular IPA brews. But growing hops also requires a great deal of water, along with the fertilizer and energy needed to transport the crops to brewers. To create beer varieties with the desired flavor of hops, but without the plants themselves, researchers from the lab of bioengineering professor Jay Keasling, and brewery science entrepreneur Charles Denby turned to altering the genome of yeast, another essential ingredient in making beer.

Denby, who has a doctorate in molecular and cellular biology from UC-Berkeley, started the company Berkeley Brewing Science to commercialize his research on more sustainable brewing processes in late 2016, near the end of his postdoctoral research. Berkeley Brewing Science is developing a more environmentally friendly process for making beer, particularly finding a substitute for hops. In their paper, the authors cite data showing growing demand caused sales of hops to triple over the past 10 years, but hops plants require some 100 billion gallons of water to grow each year. Essential oils in hops plants that provide their flavor can also vary a great deal, say the authors, making it difficult to achieve consistent taste quality.

Keasling, Denby, and colleagues applied the emerging genome editing technique Crispr for altering the molecular composition of brewer’s yeast to enable the making of beer without hops. Crispr — short for clustered regularly interspaced short palindromic repeats — is a process based on bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. The actual editing of genomes with Crispr employs enzymes that cleave DNA strands at the desired points, with Crispr-associated protein 9, or Cas9, being the enzyme used most often.

In this case, the researchers use Crispr to add genes to brewer’s yeast that provide instructions for cells to produce flavors, as well as other genes from yeast and Cas9 for the editing. The “hop flavor” genes, known as linalool synthase and geraniol synthase, came respectively from mint and basil. The inserted yeast genes provide instructions for precursor enzymes needed for yeast to produce the hop-like flavors. Crispr edited the brewer’s yeast genome to include the added genes, with the team adjusting the linalool and geraniol quantities with specialized software in a number of iterations to match those of a nearby commercial brewer.

The researchers asked food scientist and brewing expert Charles Bamforth at University of California in Davis to brew 3 batches of beer with the genome-edited yeast, after an early-stage substance known as wort is produced. Wort is unfermented beer that uses hops to produce the bitterness in beer, but without the flavor. Later brewing processes add the hop flavors, in this case from the genome-edited yeast rather than more hops.

Bamforth recruited a former student now working at Lagunitas brewery in Petaluma, California to enlist a group of fellow employees to test the 3 genome-edited beers against 2 standard freshly-made brews in a double-blind taste test. The panel said the genome-edited yeast beers had a more hoppy taste than the standard beers. “This was one of our very first sensory tests,” says co-first author and doctoral candidate Rachel Li in a university statement, “so being rated as hoppier than the two beers that were actually dry-hopped at conventional hopping rates was very encouraging.”

Denby’s company, Berkeley Brewing Science, aims to advance more sustainable brewing techniques into the marketplace. In June, the company received a $225,000 Small Business Innovation Research grant from National Science Foundation to determine the technical and commercial feasibility of these processes.

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