pIron-sulfur FeS centers are essential protein cofactors in all forms of life. They are involved in many key biological processes. In particular, Fe-S centers not only serve as enzyme cofactors in catalysis and electron transfer, they are also indispensable for the biosynthesis of complex metal-containing cofactors. Among these cofactors are the molybdenum Moco and tungsten Wco cofactors. Both MocoWco biosynthesis and Fe-S cluster assembly are highly conserved among all kingdoms of life. After formation, Fe-S clusters are transferred to carrier proteins, which insert them into recipient apo-proteins. MocoWco cofactors are composed of a tricyclic pterin compound, with the metal coordinated to its unique dithiolene group. MocoWco biosynthesis starts with an Fe-S cluster-dependent step involving radicalS-adenosylmethionine SAM chemistry. The current lack of knowledge of the connection of the assemblybiosynthesis of complex metal-containing cofactors is due to the sheer complexity of their