Caption: Two new studies explain why nitrogenases that contain the metal molybdenum are the most efficient at converting nitrogen gas into ammonia.
Image Credit: MIT News; iStock
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Scientific Frontline: Extended "At a Glance" Summary: Molybdenum-Dependent Nitrogenases
The Core Concept: Nitrogenases containing the metal molybdenum are the most efficient enzymes for converting atmospheric nitrogen gas into biologically usable ammonia.
Key Distinction/Mechanism: While molybdenum does not bind directly to nitrogen, its large atomic orbitals overlap with those of nearby iron atoms. This facilitates a process known as "back-bonding," which alters the iron's electron density, allowing it to strongly bind to and pass electrons to the nitrogen molecule to initiate the cleavage of the strong nitrogen-nitrogen triple bond.
Origin/History: Microbes evolved the enzymatic capacity to fix nitrogen approximately three billion years ago, ending the biological reliance on high-energy events like lightning strikes. The molecular mechanics explaining molybdenum's superior catalytic role were detailed in two Chem papers published in July 2026 by researchers at the Massachusetts Institute of Technology.
Major Frameworks/Components:
- Catalytic Cofactors: Clusters of iron, sulfur, carbon, and often another metal located within the active site of the enzyme.
- Molybdenum and Tungsten: Large transition metals that enable strong nitrogen binding by iron, contrasting with smaller, less efficient metals like vanadium or chromium.
- Back-Bonding: An electron-sharing mechanism where iron donates electrons to the highly resistant nitrogen molecule, a process enabled by the adjacent molybdenum atom.
- N-heterocyclic Carbenes: Chemical compounds utilized by researchers as structural models for nitrogen gas to study electron acceptance during chemical bond breaking.
Branch of Science: Biochemistry, Inorganic Chemistry, and Evolutionary Biology.
Future Application: These findings could guide the engineering of synthetic catalysts and designer enzymes capable of producing ammonia industrially or biologically, utilizing significantly less energy than the traditional Haber-Bosch process.
Why It Matters: Unlocking the exact molecular mechanism behind natural nitrogen fixation paves the way for sustainable fertilizer production, which is essential for scaling global agricultural output while minimizing environmental energy consumption.
Nitrogen gas is abundant in Earth’s atmosphere, but most living organisms cannot readily use this nitrogen. Only a subset of microbes possessing enzymes known as nitrogenases can break nitrogen gas apart and convert it into ammonia.
Three distinct classes of nitrogenases exist in nitrogen-fixing microbes, varying based on the types of metal they contain. Nitrogenases containing the metal molybdenum are the most efficient, and two new studies from MIT offer an explanation for this phenomenon.
The findings could help guide the design of engineered enzymes or synthetic catalysts that can convert nitrogen gas to ammonia, the researchers note.
The team found that while molybdenum does not directly bind to nitrogen, it helps nearby iron atoms bind to nitrogen more strongly. This is a critical first step in breaking the bond between the two nitrogen atoms that form nitrogen gas.
“It’s that initial binding step that’s really the hard part. Once you’ve started to break the nitrogen–nitrogen triple bond and make some new nitrogen–hydrogen bonds, it’s pretty easy to get the rest of the way,” says Daniel Suess, the Arthur Amos Noyes Associate Professor of Chemistry at MIT and a senior author of both papers.
MIT postdoctoral researcher Tong Wu and former postdoctoral researcher Madeleine Ehweiner are the lead authors of one of the papers, and Alexandra Brown, PhD, is the lead author of the other. Kyle Lancaster, a professor of chemistry at Cornell University, is a senior author of the latter paper, along with Suess. Both papers appear today in the journal Chem.
Efficient Enzymes
Before microbes evolved the ability to fix nitrogen approximately 3 billion years ago, the strong triple bond between atoms of \(N_2\) could only be split by high-energy events, such as a lightning strike.
“Once an enzyme came along that could convert dinitrogen to ammonia, that changed the game because now cells could harvest nitrogen from the air for biomass,” Suess says.
Within the active site of a nitrogenase is a catalytic cofactor that typically consists of a cluster of iron, sulfur, carbon, and, in some cases, another metal. Nitrogenases whose cofactors contain molybdenum are the most efficient, followed by those containing the metal vanadium. Nitrogenases that do not have any metal other than iron are the least efficient.
Why the molybdenum-containing enzyme is more efficient has been a puzzle, especially because researchers believe that molybdenum itself does not bind directly to nitrogen gas.
“In all cases, iron is thought to interact with \(N_2\), so it’s a bit of a mystery,” Suess says. “If all the chemistry is happening at iron, why is it that this molybdenum is affecting catalysis?”
To answer this question, Suess’s lab developed simpler versions of iron-sulfur clusters that can be used to model the naturally occurring cofactors. These can be modified by adding different metal atoms, allowing researchers to study how those metals change the cofactors’ properties.
In the first paper, led by Wu and Ehweiner, researchers substituted different metal atoms and then measured the ability of the iron in the cofactor to bind to nitrogen. They found that only cofactors with a large metal atom, such as molybdenum or tungsten, were able to strongly bind \(N_2\). With vanadium, chromium, or iron, which are smaller, the cofactors did not bind \(N_2\) and instead facilitated other reactions.
“That paper essentially recapitulates what you see in biology, which is that the iron-sulfur clusters that have molybdenum in them seem to be better at binding dinitrogen than those with lighter metals,” Suess says.
Sharing Electrons
In the second paper, led by Brown, the researchers uncovered a possible mechanism that explains this phenomenon.
They studied how cofactors containing different metals interact with compounds called N-heterocyclic carbenes. These molecules behave similarly to \(N_2\) in some ways, making them a good model for this type of study. Like \(N_2\), they are resistant to accepting electrons from another molecule, which is an essential step in breaking chemical bonds.
The researchers found that when molybdenum was included in the cluster, it became easier for iron to donate some of its electrons to the N-heterocyclic carbenes in a process known as back-bonding. This occurs because molybdenum, a large atom, has large orbitals that can overlap with the orbitals of the nearby iron atom. This overlap alters iron’s electron density in ways that make it easier for iron to pass electrons to \(N_2\).
“Without these direct metal–metal interactions, the iron has to do all the work, but adding the molybdenum allows for this electronic cooperativity,” Suess says.
Once \(N_2\) binds to an iron atom, the rest of the reaction can proceed. A proton can enter from water or another source to create an N–H bond, which then makes it much easier for the remaining N–N bonds to break and bind to protons, forming \(NH_3\).
The findings could help guide scientists working on designing enzymes that could be engineered into organisms to help them generate their own \(NH_3\), eliminating or reducing the need for fertilizer. The results could also help chemists design synthetic catalysts capable of producing ammonia industrially using less energy than the Haber-Bosch process.
“The general principle is that you can make an iron site in any context behave differently when you have these metal–metal interactions than when you don’t have these interactions,” Suess says. “The primary result of these findings is to teach us about the natural world and how nature accomplishes this really important and miraculous reaction. And maybe that can be translated into new processes.”
Funding: The research was funded primarily by the US Department of Energy, the National Science Foundation, and the National Institute of General Medical Sciences.
Published in journal: Chem (1 and 2)
Title:
- The influence of heterometals on dinitrogen binding at synthetic iron-sulfur clusters
- Molybdenum doping enhances backbonding at neighboring iron centers in iron-sulfur clusters
Authors:
- Tong Wu, Madeleine A. Ehweiner, Alexandra C. Brown, Alex McSkimming, and Daniel L.M. Suess
- Alexandra C. Brown, Samantha N. MacMillan, Alex McSkimming, Denis Leshchev, Eli Stavitski, Kyle M. Lancaster, and Daniel L.M. Suess
Source/Credit: Massachusetts Institute of Technology | Anne Trafton
Edited by: Scientific Frontline
Reference Number: bchm073026_01
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