[Report] Biosynthesis of a broad-spectrum nicotianamine-like metallophore in Staphylococcus aureus
Metal acquisition is a vital microbial process in metal-scarce environments, such as inside a host. Using metabolomic exploration, targeted mutagenesis, and biochemical analysis, we discovered an operon in Staphylococcus aureus that encodes the different functions required for the biosynthesis and trafficking of a broad-spectrum metallophore related to plant nicotianamine (here called staphylopine). The biosynthesis of staphylopine reveals the association of three enzyme activities: a histidine racemase, an enzyme distantly related to nicotianamine synthase, and a staphylopine dehydrogenase belonging to the DUF2338 family. Staphylopine is involved in nickel, cobalt, zinc, copper, and iron acquisition, depending on the growth conditions. This biosynthetic pathway is conserved across other pathogens, thus underscoring the importance of this metal acquisition strategy in infection. Authors: Ghassan Ghssein, Catherine Brutesco, Laurent Ouerdane, Clémentine Fojcik, Amélie Izaute, Shuanglong Wang, Christine Hajjar, Ryszard Lobinski, David Lemaire, Pierre Richaud, Romé Voulhoux, Akbar Espaillat, Felipe Cava, David Pignol, Elise Borezée-Durant, Pascal Arnoux