Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Collection des Cyanobactéries, Département de Microbiologie, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Cedex 15, 75015 Paris, France.
Science. 2018 Feb 16;359(6377):779-782. doi: 10.1126/science.aao0157.
Current textbook knowledge holds that the structural scope of ribosomal biosynthesis is based exclusively on α-amino acid backbone topology. Here we report the genome-guided discovery of bacterial pathways that posttranslationally create β-amino acid-containing products. The transformation is widespread in bacteria and is catalyzed by an enzyme belonging to a previously uncharacterized radical -adenosylmethionine family. We show that the β-amino acids result from an unusual protein splicing process involving backbone carbon-carbon bond cleavage and net excision of tyramine. The reaction can be used to incorporate diverse and multiple β-amino acids into genetically encoded precursors in In addition to enlarging the set of basic amino acid components, the excision generates keto functions that are useful as orthogonal reaction sites for chemical diversification.
现行教科书知识认为核糖体生物合成的结构范围完全基于α-氨基酸主链拓扑结构。在这里，我们报告了通过基因组指导发现的细菌途径，这些细菌途径可以在后翻译过程中产生含有β-氨基酸的产物。这种转化在细菌中广泛存在，由一种属于以前未被描述的激进-腺苷甲硫氨酸家族的酶催化。我们表明，β-氨基酸是通过一种不寻常的蛋白质剪接过程产生的，该过程涉及主链碳-碳键的断裂和对酪胺的净切除。该反应可用于将多种不同的β-氨基酸掺入基因编码的前体中。除了扩大基本氨基酸成分的集合外，这种切除还产生了酮基官能团，可作为化学多样化的正交反应位点。
