Sheref S. Mansy, Ph.D.

Associate Professor of Biochemistry, University of Trento

SCOL Project: Prebiotic iron-sulfur peptides

Modern-day metabolism is heavily dependent on metal ions. Metals such as iron, copper and zinc are required to drive metabolism. If metals are so important to life and since Earth is rich in metals, it seems plausible that the chemistry that led to life heavily exploited metals. The problem is that most of metabolism is mediated by large, complex, sophisticated proteins that incorporate and exploit these metal ions. Such proteins are the products of evolution, i.e., the products of living things. It is highly unlikely that such proteins existed on the Earth before there was life. So how could these metal ions have been exploited if there were no proteins present? The leading theory to answer this question has been rocks. Metal containing minerals (or rocks) are thought by many to have played the same role on the prebiotic Earth as contemporary proteins. While it is true that rocks can participate in chemical reactions and likely impacted the types of molecules that existed on the prebiotic Earth, there is no explanation from such theories on how proteins (or even life) could have emerged from rock. We have begun to demonstrate what we believe to be a much more plausible alternative. Prebiotic peptides can form complexes with metal ions in a way that mimics quite well modern protein enzymes. These tiny model prebiotic peptides mediate some of the same types of chemical transformations that are required for metabolism. Importantly, the formation of these iron-sulfur peptide complexes is facilitated by sunlight, a source of energy that was readily available on prebiotic Earth. We are continuing this work by exploring the metabolic-like activity of model prebiotic peptides and how such peptides could have evolved into modern-day proteins.

Sheref Mansy is an associate professor of biochemistry at the University of Trento. He received his B.S. and Ph.D. degrees from Ohio State University where he worked on the bioinorganic chemistry of metalloproteins with a focus on the biosynthesis of iron-sulfur clusters. He then carried out postdoctoral studies in Jack Szostak’s laboratory at Massachusetts General Hospital on protocells. After winning a career development award from the Armenise-Harvard foundation, he began constructing artificial cells that can chemically communicate with natural living cells and investigating the prebiotic chemistry of iron-sulfur peptides. He is a TED Fellow, a SCOL investigator since 2013 and the coordinator of a prebiotic chemistry training network for Ph.D. students in Europe.

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