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The power duo creating the future of sustainability

The Circe team's proprietary microbes consume greenhouse gases to produce dairy substitutes with better flavors and textures, making food more sustainable

By Jessica Leff

The power duo creating the future of sustainability
Wyss Institute Research Scientists Shannon Nangle, Ph.D. and Marika Ziesack, Ph.D. are working to bring the Circe technology out of the lab. Credit: Wyss Institute at Harvard University

Shifting the economy from fossil fuel-based manufacturing to more sustainable bioproduction, while touted as a major goal for reducing carbon emissions, is inherently limited. Most commercial bioproduction methods rely on agriculture to produce their sugar-based feedstocks, which is inefficient, releases greenhouse gases, and causes land use dilemmas. To address this problem, the Wyss’ Circe project is a fermentation-based platform that uses engineered microbes that eat greenhouse gases to produce tailored fats called triglycerides (TAGs). Triglycerides are found throughout nature and often serve as the fat component of food, providing flavor, nutrition, and texture. Added to plant-based foods that replicate animal products, Circe’s TAGs can make more authentic animal-free meat and dairy products. Not only does this process significantly reduce the carbon footprint of food production, but it isn’t dependent on sugar’s cost fluctuations and doesn’t require the land needed to harvest sugar-rich crops. Circe was created in Pamela Silver’s lab and is being developed by Wyss Research Scientists Shannon Nangle and Marika Ziesack. These two entrepreneurs began on different paths, but when their worlds collided, a fascinating team with unique motivations and incredible determination formed. Now, they’re poised to make a huge impact on sustainable manufacturing and decrease the environmental effects of food production.

How the stars aligned: the Silver Lab

When Ziesack was in college in Germany, she participated in a synthetic biology competition that brought her to the United States for the first time. While in the U.S., she saw incredible innovation and realized that microbes have the potential to become useful tools for sustainability. Inspired, she returned to the U.S. for her Ph.D. and joined Silver’s lab in 2013 where she began working on engineering bacterial enzymes, some of which are used by microbes engineered in the Circe project today.

The power duo creating the future of sustainability
Shannon Nangle’s interest in the future of humanity led her to an interest in synthetic biology, because it can be used to develop technologies that can help people survive on other planets, like Mars. Credit: Wyss Institute at Harvard University

Nangle has always been interested in the future of humanity. After studying neuroscience and crystallography during her undergraduate and graduate years, Nangle shifted to synthetic biology for her postdoc because she argues that the same biotechnologies that can be used to address Earth’s sustainability problems could help humans survive on other planets. She believes that keeping humans alive on other planets, specifically Mars, is the best way to help humanity continue to exist and thrive. She joined Silver’s lab in 2016 and started working on the bionic leaf, an artificial photosynthesis project that uses electricity to split water molecules into oxygen and hydrogen, then uses those gases, along with CO2, to feed microbes that produce liquid fuels. “Ultimately, the reason I was so interested in the bionic leaf was that its two main consumables, water and CO2, exist in abundance on Mars. The same is true of Circe,” Nangle explains.

Nangle decided to take the bionic leaf project in a new direction. She and Ziesack focused on using gas fermentation – the microbial process of converting gases like H2 and CO2 into useful liquid or solid commodities – to find new applications for their hydrogen-eating microbes. This eventually became its own unique project: Circe. Their current focus is on using the microbes to produce TAGs, but Circe has other applications such as PHAs (polyhydroxyalkanoates) which can be used to produce biodegradable, small-carbon footprint plastics.

A perfect match: teamwork and trust

The power duo creating the future of sustainability
Marika Ziesack applies what she learned from martial arts to her work in the lab, making her more determined, eager to learn, and detail-oriented. Credit: Wyss Institute at Harvard University

They say that opposites attract, and Ziesack and Nangle’s different backgrounds and approaches certainly complement each other. Ziesack is an active early riser who has been practicing Taekwon-Do since age nine. Many of the skills she learned from martial arts have proven useful in her research. Both require being detail-oriented, persevering, and constantly learning. On the Circe team, Ziesack is the Scientific Lead. She runs experiments, designs new bacterial strains, and writes grants to fund further development of the technology.

Nangle is a cerebral night owl who enjoys reading and painting in her free time. On the Circe team, Nangle is the Executive Lead. She spends most of her time on business development and investor relationships, but still assists with the science.

“Because there’s so much trust between us, we’re able to brainstorm without worrying about how ideas will be perceived. This helps us focus and eventually reach a solution,” explains Ziesack. They’ve learned to separate tasks and play to each other’s strengths. Most importantly, they both understand the ins and outs of this technology and are devoted to its success.

The Circe approach: metabolic engineering

While most fermentation-derived food technologies use protein engineering, Nangle and Ziesack have opted to use more complex metabolic engineering to produce their ingredients. By changing the bacterial metabolic pathways, they’re able to engineer complex metabolites rather than a single protein.

The result are fats that can be specifically tailored to match naturally occurring forms, regardless of whether they are natively produced by a plant or animal. For example, dairy milk is 90% water, and the remaining 10% is 1/3 sugar, 1/3 protein, and 1/3 fat. Certain plant-based products designed to replace dairy typically don’t have the right consistency and flavor because of the focus on proteins. Fats help provide foods’ unique textures and flavors, and greatly contribute to the experience of eating a given food. As Ziesack points out, “The more people enjoy plant-based foods, the more likely they are to buy them, and the greater impact we can have on reducing industrial farming and carbon emissions.”

Out of the lab: a focus on scaling up

These may seem like difficult goals, but Nangle and Ziesack have planned how their system will adapt and scale, ensuring it can make a lasting impact. The microbes are flexible with regards to feedstocks and can use sugar as a food source during the system’s initial prototyping and rollout. Once the technology has been fully developed, it can operate solely on gas fermentation.

If you can make one thing, then that’s a science experiment – it’s flashy and it’s cool but it has little value if you cannot scale it up. For us, being able to scale is the whole reason we’re doing this. We want to bring bioproduction into high impact markets, and you can only do this if you can produce in very large volumes.

Marika Ziesack

At the same time, they will be scaling up production. Their fermentation process started in a flask, and they’ve already moved up to a bench-scale 10L fermenter. From this, they’ve learned how to grow and manage a larger quantity of microbes and products. They’ll continue to scale up, eventually reaching a point where they can collocate with a CO2 point source (such as an ethanol plant) and build a pilot plant to harvest the greenhouse gases and feed their microbes directly.

Forming a plan to scale up this technology has always been important to the team. “If you can make one thing, then that’s a science experiment – it’s flashy and it’s cool but it has little value if you cannot scale it up. For us, being able to scale is the whole reason we’re doing this. We want to bring bioproduction into high impact markets, and you can only do this if you can produce in very large volumes,” explained Ziesack.

In the years they’ve worked together, Nangle and Ziesack have already overcome numerous challenges. They pivoted from the bionic leaf to the Circe project, and within the Circe project they have pivoted applications based on market interest. When their postdoc fellowships ended, they applied for the Wyss’ Institute Project program so they could continue de-risking their technology in a supportive environment. They are prepared to face whatever obstacles come next. Nangle explains, “We have the same goals, so when solving problems at any scale is in service of those goals, coming to resolutions is relatively straightforward.” They are determined to continue working towards reducing the environmental impact of industrial farming and ultimately making bioproduction more sustainable.

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