Artificial metabolism turns waste CO2 into useful chemicals

Engineered enzymes perform metabolic reactions that do not exist in nature

Northwestern University

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In a breakthrough that defies nature, Northwestern University and Stanford University synthetic biologists have created a new artificial metabolism that transforms waste carbon dioxide (CO2) into useful biological building blocks.

In the new study, the team engineered a biological system that can convert formate — a simple liquid molecule easily made from CO2 — into acetyl-CoA, a universal metabolite used by all living cells. As a proof of concept, the engineers then used the same system to convert acetyl-CoA into malate, a commercially valuable chemical used in foods, cosmetics and biodegradable plastics.

Unlike natural metabolic routes, the new system is entirely synthetic and operates outside of living cells. The engineers built the system, called the Reductive Formate Pathway (ReForm), from engineered enzymes that performed metabolic reactions never before seen in nature.

The work marks a major advance for synthetic biology and carbon recycling, opening the door for developing sustainable, carbon-neutral fuels and materials.

The study will be published on Monday (Dec. 22) in the journal Nature Chemical Engineering.

“The unabated release of CO2 has caused many pressing social and economic challenges for humanity,” said Northwestern’s Ashty Karim, who co-led the study. “If we’re going to address this global challenge, we critically need new routes to carbon-negative manufacturing of goods. While nature has evolved several pathways to metabolize CO2, it is unable to keep up with the rapid increase in the amount of atmospheric CO2. Inspired by nature, we sought to use biological enzymes to convert formate derived from CO2 into more valuable materials. Because there isn’t a set of enzymes in nature that can do that, we decided to engineer one.”

“ReForm can readily use diverse carbon sources, including formate, formaldehyde and methanol,” said Stanford’s Michael Jewett, who co-led the study with Karim. “This is the first demonstration of a synthetic metabolic pathway architecture that can do so. By combining electrochemistry and synthetic biology, the ReForm pathway also expands possible solutions for generalizable CO2-fixation strategies. We anticipate that hybrid technologies that integrate the best of chemistry and the best of biology will provide transformative new directions for a carbon- and energy-efficient future.”

An expert in synthetic biology and biotechnology, Karim is an assistant professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and a member of the Center for Synthetic Biology (CSB). Jewett is an adjunct professor at Northwestern, founding co-director of CSB and a professor of bioengineering at Stanford.

Looking beyond nature

As researchers search for solutions to help fight the ever-warming atmosphere, many have sought to upcycle captured CO2 into valuable chemicals. Because it’s easy to make from electricity and water, formate has emerged as a promising starting point. Then, biological systems could perform the work needed to convert formate into useful materials.

But, unfortunately, living cells struggle to use formate efficiently. Only a few rare microbes can digest formate naturally, and those microbes are difficult to engineer for large-scale production.

“Cells naturally use metabolic reactions to convert one chemical into another,” Karim said. “For example, cells can take glucose, or sugar, and convert it into energy. But, in nature, nothing can turn formate into acetyl-CoA. There are some enzymes that can act on formate, but they cannot build it up into something useful. So, we started with a theoretical pathway design and the need for enzymes with functionalities that did not exist in nature.”

Testing thousands of enzymes per week

Before building the metabolic pathway, the research team needed enzymes that could perform these non-natural reactions. To rapidly express and test large numbers of enzyme variants, the team turned to cell-free synthetic biology. In this approach, scientists essentially remove a cell’s wall, collect its molecular machinery (enzymes, cofactors and small molecules) and put it all into a test tube. Scientists then can use this machinery — outside of a living organism — to make a product in a safe, inexpensive and rapid manner.

“It’s like opening the hood of a car and removing the engine,” Jewett said. “Then, we can use that ‘engine’ for different purposes, free from the constraints of the car.”

Using a cell-free system enabled the team to rapidly screen 66 enzymes and more than 3,000 enzyme variants to find the ones that worked best. This process was much faster and more flexible than using live cells, which would have been slow and laborious.

“Typically, people will test a handful of enzymes, and that takes months or more,” Karim said. “The cell-free environment enabled us to test thousands per week.”

How it works

With this process, the researchers engineered five distinct enzymes. The final pathway design comprises six total reaction steps, in which each enzyme performs one step. Together, the series of reactions successfully transformed formate into acetyl-CoA.

Much like the enzyme testing, the entire system is run outside of living cells. That means the team could precisely control enzyme concentrations, cofactors and conditions — something that’s nearly impossible to accomplish inside a living organism.

After establishing the system, Karim, Jewett and their teams used ReForm to convert acetyl-CoA into malate. The team also demonstrated ReForm can accept other carbon-based inputs, including formaldehyde and methanol.

“From here, we can imagine this work going in a couple different directions,” Karim said. “We would like to further optimize this pathway and explore other designs to make one-carbon conversions more efficient. We also can imagine using the tools that we developed to engineer all kinds of other new enzymes and pathways. It gives us hope for a future where we can combine multiple technologies, both biological and abiological, in unique ways to find new solutions.”

The study, “A synthetic cell-free pathway for biocatalytic upgrading of formate from electrochemically reduced carbon dioxide,” was supported by the U.S. Department of Energy (award number DE-SC0023278) and the National Science Foundation. 

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Journal

Nature Chemical Engineering

DOI

10.1038/s44286-025-00315-6 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

A synthetic cell-free pathway for biocatalytic upgrading of formate from electrochemically reduced carbon dioxide

Article Publication Date

22-Dec-2025

 

Ancient sea anemone sheds light on animal cell type evolution

By mapping regulatory DNA cell by cell, researchers show how an ancient animal builds diverse cell types, and why gene control, not genes alone, drives evolution

Center for Genomic Regulation

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image: 

Nematostella vectensis, 6 mm. SERC, Rhode River, Edgewater, Ann Arundel County, MD 

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Credit: Robert Aguilar, Smithsonian Environmental Research Center

One of the biggest quests in biology is understanding how every cell in an animal’s body carries an identical genome yet still gives rise to a kaleidoscope of different cell types and tissues. A neuron doesn’t look nor behave like a muscle cell but has the same DNA.

Researchers think it comes down to how cells allow different parts of the genome to be read. Controlling these permissions are regulatory elements, regions of the genome which switch genes on or off. A detailed overview of how they do this is largely restricted to a handful of classic model organisms like mice and fruit flies.

For the first time, researchers have created a map which explains how the genome gives rise to different cell types in the starlet sea anemone, Nematostella vectensis.

Sea anemones, together with jellyfish and corals, belong to a group of animals called cnidarians. These are among the earliest animals in evolutionary history, first appearing on Earth around half a billion years ago.

The study systematically dissects the “regulatory logic” that defines cell identity in the sea anemone Nematostella. Rather than describing cell types through genes the atlas describes the regulatory elements that builds and maintains them instead. The study offers a glimpse of what sequence information in the genome encodes for the concerted activity of these regulatory networks.

The map, published today in Nature Ecology and Evolution, allows for the comparison of cell types in a different way. Grouping cells by which genes are active helps classify cells by function. But surprisingly, grouping them by regulatory elements instead tell us their developmental history, explaining from which embryonic germ layer they originated during development. That insight opens the door to exploring how similar cell types can arise from different germ layer origins, not only in development, but also during evolution.

For example, the study looked at two types of muscle cells which look similar, contract in similar ways and use almost the same genes, despite originating from different embryonic layers. The atlas revealed the genes in these cells are controlled by completely different regulatory elements.

“Expression tells us what cells do, but regulatory DNA tells us where they come from, how they develop, and which germ layer they originate from,” explains Dr. Marta Iglesias, postdoctoral researcher at the Centre for Genomic Regulation and co-first author of the study.

“Our work highlights the power of combining single-cell genomic readouts with deep learning sequence models to decode the regulatory information contained in these genomes” adds Dr. Anamaria Elek, postdoctoral researcher at the Centre for Genomic Regulation and co-first author of the study.

Cnidarians are among the earliest animals to have neurons and muscle cells, and they also feature a unique cell type called cnidocytes. These cells contain tiny, harpoon-like structures that are used to capture prey and defend against predators, as well as the stinging sensation we feel when we touch a jellyfish or sea anemone.

For evolution, gene regulation networks are a creative tool. It means new cell types and tissues can emerge from changing gene regulatory switches alone. This could make it easier for complex cell diversity to evolve, even early in animal history. The work lays the foundation for showing how the cell type which give jellyfish and anemones their characteristic sting emerged in the first place.

As the research community builds more atlases of regulatory networks in other animals in the tree of life, including species that lack cnidocytes, they can start asking what parts of that circuitry are ancient, what parts are new, and what changed as new cell types emerged.

“This study opens a whole new world of possibilities. Going forward, we will investigate animal cellular evolution by comparing genomic sequence information, and for the first time, we can do so systematically and at scale,“ says ICREA Research Professor Arnau Sebe-Pedrós at the Centre for Genomic Regulation in Barcelona.

The researchers built the map by studying 60,000 individual cells from the sea anemone’s body. They obtained them from two different life stages, around 52,000 from whole adult animals and 7,000 from gastrula-stage embryos, an early moment in development when the basic body plan is still being set up. From that, they constructed a detailed catalogue of 112,728 regulatory elements.

The scale of the discovery is surprising, given Nematostella vectensis has a genome about 269 million DNA letters long. It substantially exceeds previous estimates and approaches the same number of regulatory elements reported in the fruit fly Drosophila, which has a similar genome size of around 180 million DNA letters, but is part of a lineage that didn’t appear on Earth until hundreds of millions of years later.

The finding suggests the toolkit for genomic regulation in complex animals existed long before actual complex bodies did. The rules which let our neurons fire and muscles contract today were already in place many hundreds of millions of years ago in animals drifting in ancient seas.

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Journal

Nature Ecology & Evolution

DOI

10.1038/s41559-025-02906-1 

Method of Research

Experimental study

 

How climate policies that incentivize and penalize can drive the clean energy transition

Study finds that when clean energy incentives are applied consistently, the economy can reach an 80% reduction in energy-related carbon emissions by mid-century

University of California - San Diego

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A new study from a team of researchers that includes faculty from the University of California San Diego and Princeton University shows how a mix of subsidies for clean energy and taxes on pollution can significantly reduce greenhouse gas emissions that cause climate change.

While these kinds of policy mixes are widely used in the real world, the the study, published in Nature Climate Change is the first to show how the combination of such policies can be simulated in economic models that are the backbone of nearly all climate policy discussions – including the recent United Nations Climate Change Conference in Brazil held Nov. 10-21.  

The results reveal that financial incentives can spark rapid adoption of cleaner technologies in the near term, but without policies that also punish polluters it won’t be possible to stop climate change.  

“This work helps make our climate models more realistic about how governments actually behave,” said the study’s coauthor David Victor, professor at the School of Global Policy and Strategy and co-director of UC San Diego’s Deep Decarbonization Initiative (D2I). “For years, models have told us what’s economically efficient — but not what’s politically possible. Our goal is to bridge that gap so policymakers can craft strategies that survive real-world politics.”

The research provides a rigorous, data-driven look at how policy design and political timing affect the nation’s ability to decarbonize its energy system. 

A study arriving at a critical moment

The study comes out at a pivotal time for U.S. and global climate policy. The transition to a new U.S. administration in 2025 has cast uncertainty on many clean energy incentives enacted under the Inflation Reduction Act (IRA). At the same time, the federal government has never implemented a meaningful tax on warming pollution, although some states have adopted small tax-like policies.  

“In the United States, we are removing the reward policies designed to accelerate decarbonization and it's unlikely this administration will introduce any policies that punish larger emitters,” Victor said. “ Meanwhile, other countries are taking different paths — China is adding new incentives and some penalties and Europe is leaning heavily on policies that make emissions more expensive. You’re seeing a global experiment in real time.”

He notes that the paper, while focussing on the U.S., can serve as a “road test” for other nations around the world about which mix of policies will have the biggest impacts reducing fossil fuels. 

Testing policy sequences: rewards, penalties and political timing

The paper’s modeling also explores what happens when climate policies are added, delayed, or repealed over time. To test how such policy choices shape long-term progress, Victor and coauthors used a multisector, state-level energy systems model (GCAM-USA) to simulate how different approaches affect emissions, technology costs and clean energy adoption across all 50 U.S. states through 2050.

Using real data from federal and state programs, the researchers compared scenarios such as:

• Incentives only — Long-term subsidies that make renewable energy and electric vehicles more affordable.

• Penalties only — Economy-wide carbon pricing that makes fossil fuels more expensive.

• Combined approaches — Starting with incentives, followed by penalties after 10 or 20 years.

• Inconsistent policies — Reflecting political instability, with incentives that start, stop and restart over time.

In simpler terms, the researchers created a set of “what-if” policy simulations. Using the "carrot and stick" metaphor that refers to the set of policies of  rewards and punishments to encourage decarbonization, the authors describe what happens in a world with “no stick, more carrot,” versus “more stick, less carrot,” or policies that change mid-course.

“As ‘carrots’ make it cheaper for companies and consumers to adopt green technologies, those technologies see greater uptake,” they write. “Introducing ‘sticks’ is essential to reach deep decarbonization goals in the long run.”

The researchers were surprised by how effective incentives can be at accelerating the clean energy transition in the near term. These policies include tax credits for electric vehicles and renewable power, government grants and loans for clean manufacturing and rebates that help homeowners install heat pumps, rooftop solar panels and energy-saving upgrades.

Consistency will make energy greener and cheaper in the long run 

The study also finds that political consistency — keeping incentive programs stable and reliable — is just as important as the size of the subsidies or the stringency of future penalties. When incentives are applied consistently, the researchers found the economy can reach an 80% reduction in energy-related carbon emissions by mid-century. When those incentives are withdrawn or delayed, investment slows and later emissions cuts become more expensive.

“When policy is unpredictable, companies delay investment,” Victor said. “That delay can make it politically and economically harder to act later.”

Bringing political realism — and durability — into climate models

Victor describes the study as part of a broader research agenda at UC San Diego’s Deep Decarbonization Initiative to make climate models more attuned to real-world politics and human behavior. This extension of the initiative involves scholars from around the country, many of whom served as coauthors on this paper. 

“For years, analysts and reality have been drifting apart,” he said. “This work is part of a larger mission to make studies of climate policy much more realistic about what happens in the real world — how government policies affect investments and emissions.”   

The authors hope the research can be used as a guide for key decision makers around the globe. They conclude,  “Understanding what works — and when — is key to reaching global climate goals.”

The lead author is Huilin Luo of Princeton University and the corresponding author is Wei Peng also of Princeton University. Additional coauthors include Allen Fawcett and Gokul Iyer of the University of Maryland; Jessica Green of the University of Toronto; Jonas Meckling of the University of California, Berkeley and Harvard University; and Jonas Nahm of Johns Hopkins University.

Read the full paper, “Modelling the impacts of policy sequencing on energy decarbonization.”

 

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Journal

Nature Climate Change

DOI

10.1038/s41558-025-02497-6 

Method of Research

Computational simulation/modeling

Article Title

“Modelling the impacts of policy sequencing on energy decarbonization.

Article Publication Date

22-Dec-2025