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Getting closer to a greener world

The Circe team is making strides toward decarbonizing food production with fermentation

By Lindsay Brownell

Getting closer to a greener world
The Circe project is led by Research Associate, Shannon Nangle, Ph.D. (left), and Research Scientist, Marika Ziesack, Ph.D. (right), who are passionate about using microbes to solve some of the world’s most challenging problems. Credit: Wyss Institute at Harvard University

It sounds like science fiction: tweak the metabolism of microbes so that they can consume greenhouse gases and produce carbon-neutral products. But the Circe team of Shannon Nangle, Ph.D. and Marika Ziesack, Ph.D. is well on its way to making this dream a reality.

Initiated in 2017 in the lab of Wyss Core Faculty member Pam Silver, Ph.D., Circe has been designated a Wyss Institute Project based on its potential to drive significant improvements in sustainability. Since then, the technology’s promise has been gaining accolades and investment beyond the Wyss Institute’s walls.

A big bet on fixing fermentation

In May 2021, the US Department of Energy’s Advanced Research Projects Agency-Energy (ARPA-E) chose Circe as one of 15 research projects funded through its “Energy and Carbon Optimized Synthesis for the Bioeconomy” (ECOSynBio) program. ECOSynBio aims to slash carbon emissions and scale up the volume and efficiency of renewable bioproduction. The Circe team received nearly $3 million to support development of its system to produce carbon-neutral products via engineered microbes.

Bioproduction is a greener alternative to fossil fuel-based manufacturing because it uses organic materials, most often plants, as a source of carbon-rich sugars to produce desired products via a process called fermentation. But fermentation produces carbon as a byproduct, up to ⅓ of which is “lost” as carbon dioxide (CO2) that is not incorporated into the final product. This further exacerbates the problem of excess greenhouse gases and reduces the economic viability of many bio-based manufacturing processes. ECOSynBio’s funded projects are addressing the critical need for new bioproduction processes that reduce carbon waste and maximize the amount of renewable chemical yields.

“Biological manufacturing techniques like fermentation evolved to be very energy-efficient, but because our economy runs on carbon-based products, humans have created a situation in which we need to figure out how to do things carbon-efficiently so that we don’t just reduce carbon emissions, we actually capture all that carbon and direct it into the products we need,” said David Babson, Ph.D., a Program Director at ARPA-E. “The ECOSynBio program was created in recognition that we have to use synthetic biology to re-engineer and rethink conversion pathways to be carbon-efficient, creating a renewable circular bioeconomy.”

Getting closer to a greener world
The Circe system uses microbes to convert greenhouse gases into useable fats via gas fermentation. This process can minimize the carbon footprint of food production, and also has potential use in personal care and packaging products. Credit: Wyss Institute at Harvard University

Circe offers a way to achieve those ambitious goals. Its platform eschews plants as an input in favor of CO2 itself, avoiding the massive amounts of agricultural land that plants require. Circe’s proprietary microbes have been genetically engineered to transform CO2 and hydrogen gas into valuable carbon-based compounds within their cells via fermentation, consuming the input CO2 rather than emitting it.

“What really sets the Circe project apart is that its microbes have the ability to use both sugars and gases as feedstocks, so they can be used as part of the transition away from plant-based fermentation to gas-based fermentation. And, they don’t produce alcohol [like typical fermentation does], they produce lipids, which can be used to manufacture a different suite of chemicals and fuels,” said Babson. As part of the award, the Circe team will have quarterly meetings with ARPA-E to review their progress toward meeting ambitious metrics, targets, and timelines during the three years of the program.

“This award from ECOSynBio is huge for us because it really validates our idea that gas-based fermentation is a solution for large-scale decarbonization,” said Nangle, who is a Research Associate at the Wyss Institute.

Fueling the future of food

Just one month later, Nangle and Ziesack were named 2021 Activate Fellows. For the next two years, they will be embedded in a world-class entrepreneurial network and receive funding, mentorship, and resources to support their efforts to bring their groundbreaking research to market. As a first proof-of-concept, they plan to develop their microbe-based gas fermentation system to address problems in global food production.

The time is now for new biomanufacturing platforms to serve society, and we found Circe’s approach of using synthetic biology to create microbes that can do new jobs to be deeply compelling.

Aimee Rose, Ph.D., Managing Director of Activate Boston

“The time is now for new biomanufacturing platforms to serve society, and we found Circe’s approach of using synthetic biology to create microbes that can do new jobs to be deeply compelling,” said Aimee Rose, Ph.D., Managing Director of Activate in Boston. “The team’s demonstrated ability to rapidly tailor and scale new microbes also positions them well to address initial and future markets while delivering carbon-neutral or even carbon-negative solutions. This capability, coupled with increasing consumer demand for climate-friendly food, means they have the right tech for the right market at the right time.”

Foods rich in fats.  Main food group - macronutrient fats. Panorama, banner
Circe can manufacture a variety of different dietary fats that can be tailored for numerous food products. These fats retain the same nutritional, texture, and flavor profile as fats derived from plant and animal sources, with much lower environmental impact. Credit: Shutterstock

Nangle and Ziesack’s initial focus is on tailored fats called triglycerides (TAGs). “TAGs form the basis of most fats in foods, and are vital to their flavor, texture, and nutrition. Manufacturing these fats from microbes rather than carbon-intensive farming of plants and animals could significantly reduce the carbon footprint of food production, and make plant-based versions of foods taste more like the real thing,” said Ziesack, who is a Research Scientist at the Wyss Institute.

Over the next year, the Circe team plans to use its newly acquired resources to prioritize scaling up its fermentation technology. Their goal is to create fermenters that are large enough to be installed at CO2 sources such as ethanol plants and breweries, where they can harvest greenhouse gases and feed their microbes directly. Though not a current focus but a testament to the platform’s potential, the Circe team has also successfully produced a type of biopolymer called PHAs (polyhydroxyalkanoates) from CO2, which can be used to make biodegradable plastics.

“I am so proud of Shannon and Marika’s progress with Circe. It takes a lot of creativity, grit, and perseverance to transform something that works in a test tube at a lab bench into something that will work at a larger scale in the real world, and the two of them have been models of commitment to their goal of deploying the power of microbes to improve the health of our planet. I’m excited to see what the next chapter of their work on this project has in store,” said Pam Silver, who is also the Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology at Harvard Medical School.

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