Carbon dioxide isn’t just a climate villain. It’s also a missed opportunity.

The atmosphere is thick with it, industrial processes pump it out constantly, yet turning it into something valuable has remained stubbornly inefficient. A research team at Northwestern and Stanford has now built something nature never bothered to evolve: an artificial metabolism that converts CO2-derived molecules into chemical building blocks for plastics, food additives, and fuels.

The system, called ReForm, takes formate (a simple liquid made from captured carbon dioxide) and transforms it into acetyl-CoA, the molecular currency that sits at the center of every living cell’s metabolism. Published in Nature Chemical Engineering, the work demonstrates a new approach to carbon recycling that operates entirely outside living cells, giving scientists unprecedented control over each chemical step.

Engineering enzymes that outperform evolution

The researchers started with 66 candidate enzymes borrowed from bacteria and plants, but none were efficient enough for industrial use. Evolution optimized those proteins for survival, not for converting waste gas into valuable chemicals at scale. So the team built their own.

Using a cell-free testing system, they screened over 3,000 enzyme variants in a single week. That’s a pace impossible inside living cells. They could watch the chemistry happen in real time, observing clear liquids in tiny wells transform into target molecules without interference from a cell’s own survival machinery. This “open hood” method let them identify a quadruple mutant enzyme with catalytic efficiency ten times higher than anything found in nature.

The final ReForm pathway links six chemical steps and works with multiple one-carbon feedstocks: formate, methanol, even formaldehyde. As proof of concept, the team produced malate, a compound with a $600 million global market used in foods, cosmetics, and biodegradable plastics. They did it directly from sustainable inputs, bypassing the slow, messy processes that traditional biotech depends on.

“Because there isn’t a set of enzymes in nature that can do that, we decided to engineer one,” Ashty Karim explains. “We sought to use biological enzymes to convert formate derived from CO2 into more valuable materials.”

What happens when metabolism escapes the cell

Operating outside living cells changes everything. Microbes are finicky. They get poisoned by their own products, demand precise growth conditions, and evolve in unpredictable ways. Cell-free systems eliminate those constraints. The ReForm pathway runs in aerobic conditions with a minimal enzyme set, making it a strong candidate for industrial scale-up.

Karim, an assistant professor of chemical and biological engineering at Northwestern who co-led the study, sees this as part of a larger shift. “If we’re going to address this global challenge, we critically need new routes to carbon-negative manufacturing of goods,” he notes. The team is already planning to combine their biological precision with electrochemistry’s speed, creating hybrid platforms that could someday turn industrial exhaust into raw materials.

This isn’t the first attempt to recycle carbon dioxide through biology, but it might be the first to treat metabolism as something that can be redesigned from scratch rather than coaxed out of evolution’s leftovers. By exploring chemical spaces nature never needed, the researchers have built a tool that turns waste into value, one custom enzyme at a time.

Nature Chemical Engineering: 10.1038/s44286-025-00315-6

There’s no paywall here

*If our reporting has informed or inspired you, please consider making a donation. Every contribution, no matter the size, empowers us to continue delivering accurate, engaging, and trustworthy science and medical news. Independent journalism requires time, effort, and resources—your support ensures we can keep uncovering the stories that matter most to you.

Join us in making knowledge accessible and impactful. Thank you for standing with us!