Resurrected 3.2-Billion-Year-Old Enzyme Could Unlock the Origins of Life

By reconstructing ancient nitrogen-processing enzymes, scientists are uncovering new clues about how early life survived on a very different Earth.

Nitrogen is essential for life on Earth, yet most organisms cannot use it directly from the atmosphere. Scientists now believe this element may also provide important clues about how life first developed on our planet and how it might arise elsewhere in the universe.

“All living organisms need nitrogen to survive and, though it’s all around us, we can’t access it directly,” says Utah State University biochemist Lance Seefeldt. “Enzymes called nitrogenases enable nitrogen fixation, which converts nitrogen to a form plants, animals, humans, and other life forms can access. And we’re just beginning to understand the extent to which, over the Earth’s four-billion-year history, these nitrogenases have evolved.”

Seefeldt worked with USU senior scientist Derek Harris and other researchers involved in the NASA-funded Metal Utilization and Selection across Eons (MUSE) project at the University of Wisconsin-Madison. Their study used synthetic biology techniques to analyze modern nitrogenases and reconstruct versions that may resemble their ancient ancestors. The team reported the findings in the journal Nature Communications.

“Our role in the study was to characterize a library of the synthetically reconstructed ancestral nitrogenase genes,” says Harris. “Under controlled lab conditions, we measured the nitrogen isotope fractionation in the cell biomass of the engineered strains.”

A New Way to Study Early Earth

Seefeldt, professor and head of USU’s Department of Chemistry and Biochemistry, has spent more than 30 years studying how nitrogenase enzymes are structured and how they function. He says recreating ancient versions of these enzymes provides a powerful new approach for exploring the origins of life on Earth and for investigating how life might arise on other worlds.

“Until now, science has relied on ancient rock and fossils to study early life,” he says. “Our planet was vastly different billions of years ago. Modern microbes access atmospheric sources of nitrogen through nitrogenases, which are just one family of enzymes. Study of fossilized enzymes assumes ancient enzymes produced the same isotopic signatures as modern enzymes.”

By resurrecting these enzymes in the laboratory, scientists can investigate how they behaved long ago. According to Seefeldt, these reconstructed nitrogenases provide researchers with new insight into the composition of Earth’s atmosphere and environmental conditions in the distant past.

Implications for Agriculture and Space Exploration

“Understanding nitrogenases, both ancient and modern, is critical to helping us tackle current agricultural challenges in a changing climate, including areas at risk of famine due to drought and lack of access to commercial fertilizers,” he says.

Seefeldt also notes that the research may support future efforts to produce food beyond Earth. He has previously collaborated on several NASA-funded projects focused on growing crops in space and potentially on Mars.

Betül Kaçar, professor of bacteriology at the University of Wisconsin-Madison, director of the MUSE project, and corresponding author of the study, says the results improve scientists’ understanding of how life survived and evolved before oxygen-dependent organisms began dramatically altering the planet.

“The search for life starts here at home, and our home is four billion years old,” she says. “So, we need to understand our own past. We need to understand life before us, if we want to understand life ahead of us and life elsewhere.”

Reference: “Resurrected nitrogenases recapitulate canonical N-isotope biosignatures over two billion years” by Holly R. Rucker, Kunmanee Bubphamanee, Derek F. Harris, Kurt Konhauser, Lance C. Seefeldt, Roger Buick and Betül Kaçar, 22 January 2026, Nature Communications.
DOI: 10.1038/s41467-025-67423-y

Funding: NASA Astrobiology Institute

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