美国伊利诺伊大学厄巴纳-香槟分校van der Donk, Wilfred A.团队开发了以甘氨酰tRNA为氮供体的芳香胺生物合成途径。相关研究成果发表在2021年11月1日出版的国际学术期刊《自然—化学》。

自然界中的芳香胺通常以Glu或Gln作为氮供体。

该文中，研究人员报告了一种以甘氨酰tRNA为特征的途径。在吡咯环氨基醌类天然产物（如氨酰胺）的生物合成过程中，肽氨基酰tRNA连接酶将氨基酸附加到核糖体合成肽的C端。首先，AmmBTrpC在Trp-tRNA依赖性反应中添加Trp，然后黄素蛋白AmmC1对Trp的吲哚环进行三次羟基化。氧化成相应的邻羟基对苯二酚后，AmmBGlyD以Gly-tRNA依赖的方式将Gly连接到吲哚环上。随后的脱羧和水解产生氨基取代的吲哚。类似的转化由耐盐芽孢杆菌的同源酶催化。

该途径以三个以前未知的生化过程为特征，使用核糖体合成肽作为非核糖体肽延伸和化学修饰的支架，以生成氨基酸衍生的天然产物。

附：英文原文

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

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

Issue&Volume: 2021-11-01

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, AmmBTrpC 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, AmmBGlyD 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.

DOI: 10.1038/s41557-021-00802-2

Source: https://www.nature.com/articles/s41557-021-00802-2