C–S Bond Formations in Primary and Secondary Metabolism

Abstract

The formation of C–S bonds in primary metabolism are dominated by enzymes constructing the scaffolds of cysteine, cystathionine, methionine and S-adenosylmethionine. The first two use thiolates as nucleophiles and electrophilic-amino acid–pyridoxal phosphate adducts as partners. Methyl tetrahydrofolate is the one-carbon electrophilic donor to the thiol of homocysteine to form methionine. The least likely pairing is the thioether sulfur of methionine attacking C5′ of ATP in the formation of the C–S+ sulfonium bond in S-adenosylmethionine. In the biosynthesis of conditional secondary metabolites, low molecular weight natural products, the sulfur donors are cysteine, methionine and glutathione. One feature of secondary metabolites is the morphing of these building blocks into several varieties of sulfur heterocycles.