Along the way, they also helped bolster Nebraska’s research reputation through their prolific research and numerous honors; Banerjee even helped establish the National Institutes of Health-funded Redox Biology Center at the university in 2002 to explore redox metabolism and its connection to disease.
Such outstanding work received notice, and the pair eventually was recruited back to Michigan in 2007 (though Ragsdale never officially attended Michigan, he says he felt like an adopted member of Matthews’ lab, so it felt like a return trip).
Today, they continue exploring the frontiers of redox enzymology and one-carbon metabolism, though in different ways – Banerjee through studying mammalian pathways and clinical applications and Ragsdale through his work on microbial chemistry and applications in biotechnology.
“We do have joint lab meetings, so our students benefit from the shared expertise in our groups,” Banerjee says. “But over the years we have managed to keep our research aims different and maintain scientific independence.”
There were a couple of moments when they considered running a lab in parallel, she notes, but in the end they thought the management involved would be a little too complex.
“It’s kind of funny,” Ragsdale adds. “We started our relationship with a scientific collaboration, but in the 20 years since, we’ve both had independent careers; we’ve only published one Annual Reviews article together.”
|Vitamin B12 is an essential cofactor that is both reactive and rare. Research in the Banerjee laboratory is revealing how an intricate network of proteins tailor and escort the vitamin from its point of entry to its target enzymes in cells.
Molecular traffic patterns
Banerjee, who also serves as a member of the American Society for Biochemistry and Molecular Biology council, has focused her efforts on looking at how sulfur enzymes operate in the framework of a network. “What are the traffic lights that govern the flow of sulfur to help furnish cells with some very important reagents?”
In recent years, her group has been particularly interested in the trafficking of vitamin B12, an essential vitamin that requires 30 dedicated enzymes to synthesize in bacteria. Although humans only have two B12-requiring enzymes, both of which support sulfur metabolism (methylmalonyl-CoA mutase and methionine synthase), this rare vitamin is extremely important for every cell, as evidenced by a complex protein network involved in B12 trafficking.
Banerjee’s group has been busy identifying and assigning functions to the genes involved in B12 maintenance, which include chaperones that escort this highly reactive molecule to various destinations and some novel enzymes that tailor the cobalamin molecule to its enzyme-specific active form. For example, she recently solved a long-standing mystery by revealing that a B12 chaperone called MMACHC also was responsible for cleaving off the cyanide group in cyanocobalamin, the form that’s most prevalent in vitamin supplements.