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

Page N. Daniels, Hyunji Lee, Rebecca A. Splain, Chi P. Ting, Lingyang Zhu, Xiling Zhao, Bradley S. Moore, Wilfred A. van der Donk

Research output: Contribution to journalArticlepeer-review

Abstract

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, AmmBCTrp adds Trp in a Trp-tRNA-dependent reaction and the flavoprotein AmmC1 then carries out three hydroxylations of the indole ring of Trp. After oxidation to the corresponding ortho-hydroxy para-quinone, AmmBDGly 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 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. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)71-77
Number of pages7
JournalNature Chemistry
Volume14
Issue number1
DOIs
StatePublished - Jan 2022

ASJC Scopus subject areas

  • General Chemical Engineering
  • General Chemistry

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