The complete biosynthesis of the genetically encoded amino acid pyrrolysine from lysine

Pyrrolysine is the twenty-second naturally occurring amino acid, and it is required for the formation of methane from methylamines. Pyrrolysine is the last remaining natural amino acid with a poorly characterized biosynthetic pathway. Here it is shown that the radical SAM protein PylB converts lysine to 3-methylornithine, which then undergoes a PylC-catalysed condensation with another lysine to generate a product that is oxidized by PylD to generate pyrrolysine.