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Enzymology of oxidative sulfur transfers

Final Report Summary - ERGOX (Enzymology of oxidative sulfur transfers)

Ergothioneine is a small sulfur-containing metabolite that is produced by most fungi and many bacteria. For humans and other animals ergothioneine is an important micronutrient. A growing body of research implicates ergothioneine as a protectant against ailments such as inflammatory, cardiovascular or infectious diseases, cancer and neurodegeneration. In spite of these intriguing leads, the molecular mechanisms by which ergothioneine acts as a cytoprotectant are unknown. A parallel line of research suggests that pathogenic bacteria such as Mycobacterium tuberculosis depend on ergothioneine biosynthesis in order to establish infections. The ERC project ErgOX examined the chemical mechanism of ergothioneine biosynthesis in M. tuberculosis and other bacteria. Our study on the molecular structures and catalytic mechanisms of several enzymes involved in this process uncovered evidence that ergothioneine biosynthesis emerged at least three times independently in the course of natural history. These results suggest that ergothioneine is of fundamental importance for cellular survival and adaptation in a constantly changing environment.