Lethal synthesis, or suicide metabolism,^[1] is the biosynthesis of a toxin from a precursor which is not itself toxic, such as the synthesis of fluorocitrate from fluoroacetate or the synthesis of methylglyoxal from glycerol.^[2][3][4]

The term was first publicised by Rudolph Peters in his Croonian Lecture of 1951.^[5][3][6]

A 1971 study published by the Harvard Medical School identified methylglyoxal, a form of glycerol, as a product of lethal synthesis in a specific E.coli mutant.^[4] In E.coli, the synthesis of triose phosphate from glycerol is a reaction regulated by the synthesis rate of glycerol kinase and by feedback inhibition by fructose-1,6-bisphosphate.^[4] The study demonstrated that, in E.coli mutants that had lost both control mechanisms, glycerol kinase no longer reacted to feedback regulation and instead produced the cytotoxic methylglyoxal.^[4] A more recent review of research done on methylglyoxal metabolism concluded that the compound's cytotoxic nature is dependent on its ability to form advanced glycation end products (AGEs).^[7] These compounds, which are thought to be factors in ageing and in the progression of degenerative diseases, have been shown to hinder the functions of the proteins they target.^[7]