Genes behind lager yeast's cold- and sugar-loving success revealed

Lager beer is cold, crisp, dry—and worth about half a trillion dollars worldwide.

Behind the world's most popular alcoholic beverage is a yeast adapted to the cold, and hungry for the sugars it will transform into bubbles and booze.

That yeast is a hybrid, an amalgamation of the domesticated baker's yeast Saccharomyces cerevisiae and a recently discovered wild species, Saccharomyces eubayanus. Hundreds of years ago, the two species combined their strengths into a cold-fermenting strain that readily produces the crisp, light taste that came to dominate the beer market in the centuries that followed.

In a pair of new papers, University of Wisconsin-Madison Professor of Genetics Chris Todd Hittinger, his graduate student EmilyClare Baker and others show how modern lager yeast adopted the cold-loving and sugar-hungry traits essential to their success.

In one paper, to be published Feb. 1 in Science Advances, the team demonstrates that when the cold-loving S. eubayanus donated its mitochondria—the power-generating portion of the cell—to the new hybrid, it conferred cold tolerance on the strain. Today, all industrial lager strains retain the S. eubayanus mitochondria and ferment at cold temps.

In a second paper, Baker and Hittinger investigated the ability of S. eubayanus to ferment all the sugars in wort, the barley malt extract that ferments into beer. Most strains of S. eubayanus cannot ferment maltotriose, the second-most common sugar in wort. But the researchers were able to evolve a brand-new protein capable of transporting maltotriose into the cell, revealing a potential path to more aggressive fermentation of all available sugars, a key trait in producing a dry, crisp beer. The paper was published on the pre-print server bioRxiv ahead of publication in the journal PLOS Genetics.

The new research is the first to identify the genetic underpinnings of how two of the most defining features of lager production—cold tolerance and complete fermentation—evolved in S. eubayanus and its hybrid offspring. Hittinger and Baker have applied for patents based on their work, which could provide new opportunities for altering both the temperature range and sugar metabolizing ability of industrial lager strains.

In 2011, Hittinger was part of the team that first isolated S. eubayanus in the wild from forests in Patagonia. Since then, his lab has worked to uncover how S. eubayanus combined with the bread-and-ale yeast S. cerevisiae some 500 years ago to kickstart the behemoth lager beer industry. Their partners in the brewing industry and the UW-Madison food science department helped them zero in on researching the origin of two key traits: growth in the cold and churning through all the sugar in wort.

One clue to lager yeast's cold preference came from a slate of recent studies showing that temperature tolerance in a wide range of species could be linked, at least partially, to mitochondria. These cellular components generate the bulk of the energy that cells rely on and have their own genome, albeit a small one with just a handful of genes.

Baker and Hittinger had previously shown that lager yeast inherited their mitochondria from S. eubayanus. To see if these mitochondria helped lager yeast thrive at cold temperatures, Baker treated S. eubayanus or S. cerevisiae strains with a chemical that broke down the yeast's mitochondrial DNA.