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

Autor: Daniels, Page N., Lee, Hyunji, Splain, Rebecca A., Ting, Chi P., Zhu, Lingyang, Zhao, Xiling, Moore, Bradley S., van der Donk, Wilfred A.
Zdroj: Nature Chemistry; 20240101, Issue: Preprints p1-7, 7p
Abstrakt: Aromatic amines in nature are typically installed with Glu or Gln as the nitrogen donor. Here we report a pathway that features glycyl-tRNA instead. During the biosynthesis of pyrroloiminoquinone-type natural products such as ammosamides, peptide-aminoacyl tRNA ligases append amino acids to the C-terminus of a ribosomally synthesized peptide. First, AmmBCTrpadds Trp in a Trp-tRNA-dependent reaction and the flavoprotein AmmC1then carries out three hydroxylations of the indole ring of Trp. After oxidation to the corresponding ortho-hydroxy para-quinone, AmmBDGlyattaches Gly to the indole ring in a Gly-tRNA dependent fashion. Subsequent decarboxylation and hydrolysis results in an amino-substituted indole. Similar transformations are catalysed 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.
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