A biosynthetic pathway to aromatic amines that uses glycyl-tRNA as nitrogen donor

Aromatic amines in nature are typically installed with Glu or Gln as the nitrogen donor. Here we report a pathway that features glycyl-tRNA as the nitrogen donor. During the biosynthesis of pyrroloiminoquinone-type natural products such as ammosamide, peptide-aminoacyl tRNA ligases (PEARLs) append amino acids to the C-terminus of a ribosomally synthesized peptide. First, [Formula: see text] adds Trp in a Trp-tRNA dependent reaction, and the flavoprotein AmmC(1) then carries out three hydroxylations of the indole ring of Trp. After oxidation to the corresponding ortho-hydroxy para-quinone, [Formula: see text] attaches Gly to the indole ring in a Gly-tRNA dependent fashion. Subsequent decarboxylation and hydrolysis results in an amino-substituted indole. Similar transformations are catalyzed by orthologous enzymes from Bacillus halodurans. This pathway features three previously unknown biochemical processes using a ribosomally synthesized peptide as scaffold for non-ribosomal peptide extension and chemical modification to generate an amino acid derived natural product.