Abstract
Sulfur is an essential element for a variety of cellular constituents in all living organisms and adds considerable functionality to a wide range of biomolecules. The pathways for incorporating sulfur into central metabolites of the cell such as cysteine, methionine, cystathionine, and homocysteine have long been established. Furthermore, the importance of persulfide intermediates during the biosynthesis of thionucleotide-containing tRNAs, iron-sulfur clusters, thiamin diphosphate, and the molybdenum cofactor are well known. This review briefly surveys these topics while emphasizing more recent aspects of sulfur metabolism that involve unconventional biosynthetic pathways. Sacrificial sulfur transfers from protein cysteinyl side chains to precursors of thiamin and the nickel-pincer nucleotide (NPN) cofactor are described. Newer aspects of synthesis for lipoic acid, biotin, and other compounds are summarized, focusing on the requisite iron-sulfur cluster destruction. Sulfur transfers by using a noncore sulfide ligand bound to a [4Fe-4S] cluster are highlighted for generating certain thioamides and for alternative biosynthetic pathways of thionucleotides and the NPN cofactor. Thioamide formation by activating an amide oxygen atom via phosphorylation also is illustrated. The discussion of these topics stresses the chemical reaction mechanisms of the transformations and generally avoids comments on the gene/protein nomenclature or the sources of the enzymes. This work sets the stage for future efforts to decipher the diverse mechanisms of sulfur incorporation into biological molecules.