When Charles Denby looks at a pint of beer, he sees a product of one of the oldest biotechnologies in the world. Beer- and winemaking are now under threat from climate change: experts expect the taste of beer to change and prices to go up as drought and high temperatures impact the growth and supply of hops, barley, and fruit crops.
Denby hopes to reform brewing with molecular engineering. Berkeley Yeast—the start-up he cofounded in 2017 as Berkeley Fermentation Science—is engineering yeast to produce key molecules that give beers and wines distinct flavors. This should allow craft brewers and winemakers to produce bold-flavored beverages with fewer hops and less fruit. “Our mission is to create technology that’s good for people and the planet,” he says. But persuading customers that the modified yeast is safe to use in their products has taken work.
Denby spoke with Prachi Patel about the challenges involved in helping breweries and wineries become more sustainable. This interview was edited for length and clarity.
▸ Current position: Cofounder and CEO, Berkeley Yeast
▸ Hometown: Seattle
▸ Education: BA, biophysics, biochemistry, and molecular biology, Whitman College, 2005; PhD, molecular and cellular biology, University of California, Berkeley, 2012
▸ Favorite type of beer: Trumer Pils
▸ Favorite Berkeley Yeast product: Tropics, a London ale yeast that converts thiol precursor molecules into thiols with bold guava and passion fruit flavors
▸ What he does for fun: Hiking, road biking, rock climbing, and skiing
How did you and your cofounders meet, and what made you decide to launch Berkeley Yeast?
I was a postdoc in a bioengineering lab at the University of California, Berkeley, studying how to engineer microbes to make industrial products like biofuels and medicinal compounds. While there, I started making beer in my garage and found that the most expensive brewing ingredients are the hops that impart flavor to the beverage. Flavor compounds, such as terpenes, are similar to the ones that I was engineering yeast to produce.
So then-graduate student Rachel Li and I started engineering yeast to make some of those flavor molecules. We had a prototype by 2016. That’s when I met Nick Harris, who was also a graduate student at UC Berkeley interested in engineering microbes for fuels. He had worked in a brewery for a few months before grad school and had also run a small biofuels company. A Small Business Innovation Research grant from the US National Science Foundation in 2017 helped us get out of the lab and launch the company.
How does your technology work? Why is it appealing to brewers and winemakers?
A variety of compounds create the flavors that hops give to beer. Hop plants make those compounds through biosynthetic pathways. Our big idea is to insert those pathways into yeast so they can create the same flavor compounds.
With metabolic engineering, people usually engineer a microbe to make a compound or protein of interest in a fermentation tank. Then they purify the compound and add it to their product.
We’re doing something different. A key aspect of our technology is that it’s a drop-in replacement. Beer and wine already rely on yeast to turn sugars into alcohol. We add a few extra snippets of DNA into the yeast genome so it still ferments beer and wine, while adding flavor compounds to enhance the beverage. It’s a seamless transition because a brewery can switch out the yeast it already uses.
What are these flavor compounds? What kinds of genes do you need to tinker with to make new flavors?
Our first prototype technology was engineering brewer’s yeast (Saccharomyces cerevisiae) to make terpenes, which produce citrus and floral flavors (Nat. Commun. 2018, DOI: 10.1038/s41467-018-03293-x). We created three different terpenes: linalool, geraniol, and citronellol. Those were thought to be the primary determinants of hop flavors, but that’s not the full story. Many other components are also important for driving hop flavor. So since then, we’ve engineered yeast to make other classes of compounds that drive flavors. The two major ones are esters and thiols.
For some compounds, their precursor is part of the yeast’s natural metabolism, but sometimes it’s further away. For example, yeast doesn’t make the precursors of linalool at high enough levels, so you have to modify the genetic pathway that produces the precursor. One of the biggest challenges is to modify the yeast genome without adversely impacting its normal fermentation metabolism.
How does your technology make beer- and winemaking more sustainable?
Hops are resource intensive. For every pint of beer produced, 50 pints of water on average are used to irrigate the hop plants. The fertilizer use is also nontrivial. If we can replace the US hop crop with our yeast, that would be roughly equal to reducing the carbon footprint of 50,000 humans. Hops are also endangered by climate change. Most of the US crop is grown in Washington state’s Yakima Valley, which benefits from the Cascade mountains’ watershed and sunny, fairly dry climate. But climate scientists say that will not persist forever.
Hops are the essence of signature craft beers like IPAs. Do you meet pushback to replacing hops, especially with a genetically engineered product?
One cool thing about this technology being a drop-in replacement is that we can create a quarter or half of the flavor that ordinarily comes from hops. People can use the yeast to complement and enhance the flavors that are coming from hops. Our customers in the craft industry are brewers who use fermentation technology every day. They are science savvy and generally receptive to the idea of genetic engineering. They are often concerned about how it would sit with their customers, but it feels like the tide is slowly changing.
What challenges have you faced transitioning from academia to a start-up?
As a bunch of scientists serving a big industry, you’re initially received as an outsider. We originally came out and said, “This technology will replace hops.” That was not a great move because using hops is part of the tradition of brewing and nobody wants to phase out hops entirely. Since then, we’ve focused on complementing hops and also enabling the industry to use more drought-resistant varietals that will be robust to climate change. But since they might not pack the same flavor punch, you can deliver those flavors through yeast. On another note, we’ve also made a major effort to be transparent about the technology we’re developing and engage with brewers and winemakers and address their concerns.
Prachi Patel is a freelance writer in Pittsburgh who covers energy, materials science, and nanotechnology. A version of this story first appeared in ACS Central Science: cenm.ag/denby.