Scientists resurrect 3.2-billion-year-old enzyme to reveal how life began on Earth


Nitrogen is essential for every known form of life on Earth. Now, scientists say this common element may also help explain how the first life evolved on our planet and how life evolved elsewhere in the universe.

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

In a study published in nature communicationSeefeldt, USU senior scientist Derek Harris, and colleagues in the NASA-funded Metal Utilization and Selection Across Eons (MUSE) project at the University of Wisconsin-Madison used synthetic biology to work backwards from modern nitrogenases and reconstruct possible ancestral versions of these enzymes.

Reconstruction of ancient nitrogen-fixing enzymes

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

The research allowed scientists to examine how ancient nitrogenases might have functioned billions of years ago.

Seefeldt, who serves as professor and head of USU’s Department of Chemistry and Biochemistry, has spent more than 30 years studying the structure and function of nitrogenase. He says the ability to recreate ancient forms of these enzymes marks a significant advance in efforts to understand the origins of life on Earth and potentially on other worlds.

“Until now, science has relied on ancient rocks and fossils to study early life,” he says. “Billions of years ago our planet was completely different. Modern microorganisms access atmospheric sources of nitrogen through nitrogenases, which are just one family of enzymes. Studies of fossil enzymes show that ancient enzymes produced the same isotopic signatures as modern enzymes.”

New clues about the early Earth

According to Seefeldt, the reconstructed nitrogenases provide a new way to investigate what conditions may have been like on Earth and its atmosphere in the distant past.

“Understanding nitrogenase, both ancient and modern, is important to help address current agricultural challenges in a changing climate, including in areas at risk of famine due to drought and lack of access to commercial fertilizers,” he says.

The findings may have practical applications beyond Earth. Seefeldt, who has participated in other NASA-funded projects, says this work contributes to ongoing efforts to determine how food can be grown in space and on Mars.

Implications for the search for life beyond Earth

Betul Kakar, professor of bacteriology at UW-Madison, director of the MUSE project, and corresponding author of the study, says the results provide a clear view of how life survived and evolved before oxygen-dependent organisms transformed the planet.

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

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