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Biological Chemistry

Alfred Bader Award In Bioinorganic Or Bioorganic Chemistry

by Jyllian Kemsley
February 23, 2015 | A version of this story appeared in Volume 93, Issue 8


Credit: Courtesy of Michael Marletta
Michael A. Marletta; he was at Scripps and will return to UC Berkeley in summer 2015.
Credit: Courtesy of Michael Marletta

Sponsored by the Alfred R. Bader Fund

Michael A. Marletta became a chemist because of food and “the joy of figuring things out,” he says.

His father worked for R. T. French, of French’s Mustard fame. “My father would come home smelling of spices, and my mother was born in Italy and was a fantastic cook,” Marletta says. Eventually, he checked out a library book on food chemistry and discovered the natural product structures that give spices their smell and taste.

His childhood generally involved a lot of library books, sports, and science, he says. After Sputnik launched, he got a telescope for Christmas. It seldom left his hand. The following year, he got a microscope and proceeded to study a pond he created from leaves and dechlorinated tap water. Then he wanted a chemistry set. His father said no. Marletta credits that denial with cementing his interest in the subject.

Marletta majored in chemistry and biology at SUNY Fredonia. In graduate school at the University of California, San Francisco, and during postdoctoral work at Massachusetts Institute of Technology, Marletta synthesized molecules to help illuminate enzyme mechanisms.

He went on to a faculty position in biological sciences at MIT, where he planned to focus on cytochrome P450 enzymes. Then a colleague, Steven R. Tannenbaum, convinced him that mammals were making nitrate. “He said to me that there were probably some novel enzymes involved,” Marletta says. “It was really that idea that led to the discoveries we’ve made in the nitric oxide area.”

Marletta eventually established that immune system macrophages use arginine to make NO to kill pathogens; excess NO winds up excreted as nitrate. Meanwhile, other researchers demonstrated that NO plays key roles in vasodilation and neurotransmission.

“Before this time, NO biosynthesis was thought to be restricted to bacteria engaged in nitrification reactions,” says Jack E. Dixon, associate vice chancellor of scientific affairs and a pharmacology professor at UC San Diego. “The idea that higher organisms could produce this unstable, toxic, diatomic free radical was considered extremely unlikely.”

“Figuring out how NO is made and how it gets to receptors and to targets required embracing medicine, pharmacology, biochemistry, and chemistry,” Marletta says. Of his various findings, he highlights unraveling how guanylate cyclase can selectively sense NO in a sea of competing O2; he determined that NO binds more strongly to the enzyme’s heme cofactor unless the protein positions a hydrogen-bonding residue to hold O2 in place.

Marletta continues to study NO and other gas-signaling pathways in biological systems. He’s also working to understand fungal polysaccharide monooxygenases, which use copper to create nicks in cellulose. The nicks make it easier for cellulases to break down cellulose into fermentable products. The monooxygenases may also be important in human pathogen activity, Marletta says.

Over the course of his career, Marletta, now 64, moved from MIT to the University of Michigan and then to UC Berkeley before becoming president of Scripps Research Institute in 2012. He resigned that position in 2014 and remains on the Scripps faculty.

Marletta will present his award address before the Division of Biological Chemistry.


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