Dubbed “Conan the Bacterium” for its extraordinary ability to tolerate the harshest of conditions, Deinococcus radiodurans can withstand radiation doses thousands of times higher than what would kill a human — and every other organism for that matter.
The secret behind this impressive resistance is the presence of a collection of simple metabolites, which combine with manganese to form a powerful antioxidant. Now, chemists at Northwestern University and the Uniformed Services University (USU) have discovered how this antioxidant works.
In a new study, the researchers characterized a synthetic designer antioxidant, called MDP, which was inspired by Deinococcus radiodurans’ resilience. They found MDP’s components — manganese ions, phosphate and a small peptide — form a ternary complex that is a much more powerful protectant from radiation damage than manganese combined with either of the other individual components alone.
This discovery could eventually lead to new synthetic antioxidants specifically tailored to human needs. Applications include protecting astronauts from intense cosmic radiation during deep-space missions, preparing for radiation emergencies and producing radiation-inactivated vaccines.
The study will be published during the week of Dec. 9 in the Proceedings of the National Academy of Sciences.
“It is this ternary complex that is MDP’s superb shield against the effects of radiation,” said Northwestern’s Brian Hoffman, who conducted the study with USU’s Michael Daly. “We’ve long known that manganese ions and phosphate together make a strong antioxidant, but discovering and understanding the ‘magic’ potency provided by the addition of the third component is a breakthrough. This study has provided the key to understanding why this combination is such a powerful — and promising — radioprotectant.”
Hoffman is the Charles E. and Emma H. Morrison Professor of Chemistry and professor of molecular biosciences at Northwestern’s Weinberg College of Arts and Sciences. He also is a member of the Chemistry of Life Processes Institute. An expert on Deinococcus radiodurans, Daly is a professor of pathology at USU and a member of the National Academies’ Committee on Planetary Protection.
Incredible Hulk of the microbial world
The new study builds on previous research from Hoffman’s and Daly’s collaboration, during which they sought to better understand Deinococcus radiodurans’ predicted ability to withstand radiation on Mars. In that research, Hoffman’s team at Northwestern used an advanced spectroscopy technique to measure the accumulation of manganese antioxidants in the microbes’ cells.
According to Hoffman and Daly, the size of the radiation dose that a microorganism or its spores can survive directly correlates with the amount of manganese antioxidants it contains. In other words, more manganese antioxidants mean more resistance to intense radiation.
In earlier studies, other researchers discovered Deinococcus radiodurans can survive 25,000 grays (or units of x- and gamma-rays). But, in their 2022 study, Hoffman and Daly found that the bacterium — when dried and frozen — could weather 140,000 grays of radiation, a dose 28,000 times greater than what would kill a human. So, if there are any slumbering, frozen microbes buried on Mars, they possibly could have survived the onslaught of galactic cosmic radiation and solar protons to this day.
The power of three
Building on their efforts to understand the microbe’s radiation resistance, Hoffman and Daly’s team investigated a designer decapeptide called DP1. When combined with phosphate and manganese, DP1 forms the free-radical-scavenging agent MDP, which successfully protects cells and proteins against radiation damage. In another recent study, Daly and his collaborators found MDP is effective in the preparation of irradiated polyvalent vaccines.
Using advanced paramagnetic resonance spectroscopy, the team revealed that the active ingredient of MDP is a ternary complex — a precise assembly of phosphate and peptide bound to manganese.
“This new understanding of MDP could lead to the development of even more potent manganese-based antioxidants for applications in health care, industry, defense and space exploration,” Daly said.
The study, “The ternary complex of Mn2+, synthetic decapeptide DP1 (DEHGTAVMLK) and orthophosphate is a superb antioxidant,” was supported by the National Institutes of Health (grant number GM111097), the National Science Foundation (grant number CHE-2333907) and the Defense Threat Reduction Agency (grant number HDTRA1620354).
