UH OH
Researchers say resurrected ancient enzyme could explain early life on Earth and beyond
Utah State University biochemists Lance Seefeldt and Derek Harris, with University of Wisconsin-Madison colleagues in the NASA-funded MUSE astrobiology project, report findings from study of 3.2-billion-year-old nitrogenases in Nature Communications.
Utah State University
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Utah State University biochemists Derek Harris, left, and Lance Seefeldt, and and fellow colleagues with the NASA-funded Metal Utilization and Selection across Eons (MUSE) project at the University of Wisconsin-Madison, are authors of a Jan. 22 ‘Nature Communications’ paper describing breakthrough research on ancient enzymes responsible for life on Earth.
view moreCredit: M. Muffoletto, USU
LOGAN, UTAH, USA -- Nitrogen, upon which all life on Earth depends, may hold the key for explaining how early life on the planet evolved and how it could evolve on other planets.
“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, with USU senior scientist Derek Harris and fellow colleagues with the NASA-funded Metal Utilization and Selection across Eons (MUSE) project at the University of Wisconsin-Madison, report findings from a study using synthetic biology to reverse-engineer modern nitrogenases and rebuild their possible ancestors in the Jan. 22, 2026 issue of 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.”
Seefeldt, professor and head of USU’s Department of Chemistry and Biochemistry, has studied the structure and function of nitrogenases for more than three decades, says being able to reconstruct ancient nitrogenases represents a breakthrough in understanding the origins of life on Earth, as well as on other planets.
“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.”
Reconstructed nitrogenases, Seefeldt says, offer researchers a new window into what Earth and its atmosphere was like eons ago.
“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.
Additionally, Seefeldt, who has collaborated on other NASA-funded projects, says the research fuels efforts to explore how to grow food in space and on Mars.
Betül Kaçar, professor of bacteriology at the UW-Madison, director of the MUSE project and corresponding author on the paper, says study findings offer a sharper picture of how life persisted and evolved before oxygen-dependent organisms began reshaping the Earth.
“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.”
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Journal
Nature Communications
Method of Research
Experimental study
Subject of Research
Not applicable
Article Title
Resurrected nitrogenases recapitulate canonical N-isotope biosignatures over two billion years
Article Publication Date
22-Jan-2026
Resurrected ancient enzyme offers new window into early Earth and the search for life beyond it
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Betul Kacar presents samples in her lab
view moreCredit: Photo by Jeff Miller/UW–Madison
By resurrecting a 3.2-billion-year-old enzyme and studying it inside living microbes, researchers at the University of Wisconsin–Madison have created a new way to improve our understanding of the origins of life on Earth and possibly recognize signs of life elsewhere.
Recently published in Nature Communications, the NASA-funded study uses synthetic biology to reverse-engineer modern enzymes and rebuild their possible ancestors. Betül Kaçar, a professor of bacteriology, and Holly Rucker, a PhD candidate in Kaçar’s lab, focused on an enzyme called nitrogenase, which is critical to the process that converts atmospheric nitrogen into a form usable by living organisms. “We picked an enzyme that really set the tone of life on this planet and then interrogated its history,” Kaçar says. “Without nitrogenase, there would be no life as we know it.”
Historically scientists have relied on evidence found in the geological record to build our understanding of past life on Earth. Such significant fossil and rock samples arerare and often require a bit of luck to find. Kaçar and Rucker see synthetic biology as a way to augment this important work, filling in the gaps by creating tangible reconstructions of ancient enzymes, putting them into microbes, and studying them in a modern lab. “Three billion years ago is a vastly different Earth than what we see today,” says Rucker. Back before the Great Oxidation Event, she explains, the atmosphere contained more carbon dioxide and methane, and life primarily consisted of anaerobic microbes. Being able to understand how these microbes accessed a nutrient as vital as nitrogen offers a sharper picture of how life persisted and evolved in the window of time before oxygen-dependent organisms began reshaping the planet. While there are not fossilized enzymes the team can study, these enzymes can leave behind recognizable signatures in the form of isotopes, which researchers can measure in rock samples. But much of that work relied on the assumption that ancient enzymes produce the same isotopic signatures as modern versions. Rucker began to
wonder: Are we actually interpreting the rock record correctly?
“It turns out, yes, at least for nitrogenase,” Rucker says. “The signatures that we see in the ancient past are the same that we see today, which then also tells us more about the enzyme itself.” The team found that even though ancient nitrogenase enzymes have different DNA sequences than modern versions, the mechanism that controls the isotopic signature preserved in the rock record has stayed the same. Rucker hopes to investigate why the mechanism was conserved while other aspects of the enzyme evolved.
This project connects to Kaçar’s broader work as the leader of MUSE, a NASA-funded astrobiology research consortium based at UW–Madison. From astrobiologists to geologists across several institutions, MUSE brings researchers together to strengthen NASA space missions through new evolutionary insights into microbiology and molecular biology on Earth. With nitrogenase-derived isotopes now identified as a reliable biosignature on Earth, MUSE has a clearer framework for evaluating similar signals that may be found on other planets. “As astrobiologists, we rely on understanding our planet to understand life in the universe. The search for life starts here at home, and our home is 4 billion years old,” Kaçar 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.”
Journal
Nature Communications
Method of Research
Experimental study
Subject of Research
Not applicable
Article Publication Date
22-Jan-2026
