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Trent Stubbs ’20, Professor Greg Springsteen published in Nature Chemistry

Trent Stubbs '20 and Professor of Chemistry Greg Springsteen
Trent Stubbs '20, left, and Furman Professor of Chemistry Greg Springsteen.

The large majority of scientists end long and successful careers with their names never appearing on a paper published by Nature Chemistry. The number who did it while an undergraduate?

Well, let’s just say Trent Stubbs ’20, who just began pursuit of a Ph.D. in chemistry at Emory University after graduating cum laude from Furman in May, is in some very select company.

“As strange as this sounds, because I am technically in the first year of graduate school, this might be one of the biggest papers of my career, and the one I am most proud of,” said Stubbs. “This took three years of work with (Furman Professor of Chemistry Greg) Springsteen and (about) 150 drafts until we got it the way we wanted.”

Stubbs is the first author of “A Plausible Metal-Free Ancestral Analogue of the Krebs Cycle Composed Entirely of ?-Ketoacids,” which appears in the October edition of Nature Chemistry. A peer-reviewed journal dedicated to “the most significant and cutting-edge research in all areas of chemistry,” Nature Chemistry was ranked fifth in the 2019 SCImago Journal Rank indicator and is considered one of the most prestigious scientific publications in the world.

“It is absolutely one of the very top journals of chemistry, and it’s extremely difficult to publish in there. The rejection rate is very, very high,” Furman Professor of Chemistry and Department Chair Tim Hanks said. “It’s not a place that we (as a primarily undergraduate institution) typically publish.”

What caught the attention of Nature Chemistry’s editors is a discovery Stubbs made in a Furman lab that has the potential to fundamentally alter humanity’s understanding of the origin of life, specifically how organic chemical reactions could have started inorganically for the first time billions of years ago. One of those metabolic processes is called the Krebs cycle, also known as the citric acid cycle, and while it is one of the vital biological pathways it had never been replicated synthetically – until now.

“Trent started with some small molecules and figured out how to make the Krebs cycle run, and it runs without enzymes in water at mild pH,” Springsteen, the corresponding author on the paper, said. “These discoveries have potential applications in understanding how life started on Earth, and where else in the universe it may emerge.”

Being the first author indicates Stubbs led the experimental work. As corresponding author, Springsteen was responsible for initiating and managing the project. He and Stubbs wrote the manuscript together, with substantial inputs from Mahipal Yadav and Ram Krishnamurthy from The Scripps Research Institute.

“Our hypothesis was, let’s start by looking at what is fundamental to life right now. What’s in living cells? What are some of those core components that must have existed very early on? The answer is the citric acid cycle,” Stubbs said. “This is one of the processes that turns food into energy, doesn’t matter whether you’re human, plant, lizard, whatever … So it’s likely this cycle existed near the origins of life, and that’s what this paper is all about – how could simpler versions of this cycle, which now requires complex biological machinery to operate, have operated from the beginning without any of that evolved hardware?”

The paper also earned a place as the top story in Quanta Magazine as well as animated versions of Springsteen and Stubbs appearing in the most recent Stated Clearly video, “What Is The Metabolism-First Hypothesis For The Origin Of Life?”

“Other scientists hailed the significance of the new findings, as well as the originality and rigorous chemical expertise of the researchers,” Quanta deputy editor John Rennie wrote.

Founded by Jon Perry to promote a better understanding of biological evolution, the Stated Clearly project breaks complex scientific concepts down to help the general public better understand and appreciate the work. Its videos receive millions of views. The animation covers metabolism-first ideas in general and then focuses on specific research done by Springsteen and Stubbs.

The research behind the Nature Chemistry paper was the byproduct of Springsteen’s role as a theme leader for a joint National Science Foundation (NSF) and NASA research consortium called the Center for Chemical Evolution. Springsteen specializes in applying the principles of mechanistic organic chemistry to understanding life and its origins, and he and his students have been trying for more than a decade to unravel how natural chemical reactions could have evolved into a self-sustaining network of metabolic reactions, which is a central criterion for life.

Springsteen was named one of eight national Henry Dreyfus Teacher-Scholar Scholars in 2018, and federal grants he has written have brought in over $1 million in research and instrument funding to Furman over the last five years. Stubbs was named a Furman Fellow in 2019-20, which is a fellowship given annually to students who have shown unique leadership skills and an ability to make a difference in the world and in the lives of others.

Stubbs’ discovery also led to novel ways to chemically synthesize biological diagnostic agents used in an emerging cancer and a bacterial infection detection diagnostic method called metabolic flux analysis. Recognizing the commercial potential, Springsteen and Stubbs co-founded and launched Aconabolics LLC in July of 2018, which operates out of a specially constructed lab space on campus, to commercialize these results.

Springsteen and Stubbs are also the inventors on two patents that resulted from the research, which are the second and third in Furman’s history.

“We’ve had a very strong (chemistry) program for many years, many decades, really. We have records indicating undergraduates were doing research with faculty back in the late 1930s,” Hanks said. “There has been some extremely good research coming out of here … The whole department is very proud of Greg and Trent. They have done a lot of really good work to get to this stage. Trent is a very special guy, and so is Greg.”

A graphic illustrating a newly discovered chemical pathway that may be an ancestor to the Krebs cycle, which is one of the major components of life.
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