Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, United States.
ACS Chem Biol. 2011 Oct 21;6(10):1000-7. doi: 10.1021/cb200284p. Epub 2011 Aug 25.
Peptidyl nucleoside antibiotics are a group of natural products targeting MraY, a bacterial translocase involved in the lipid-linked cycle in peptidoglycan biosynthesis. In this Perspective, we explore how Nature builds complex peptidyl nucleoside antibiotics scaffolds from simple nucleoside and amino acid building blocks. We discuss the current stage of research on biosynthetic pathways for peptidyl nucleoside antibiotics, primarily focusing on chemical logic and enzymatic machinery for uridine transformation and coupling to peptides. We further survey the nonribosomal biosynthetic paradigm for a subgroup of uridyl peptide antibiotics represented by pacidamycins, concluded by diversification opportunities for antibiotic optimization.
肽核苷抗生素是一组靶向 MraY 的天然产物，MraY 是一种参与肽聚糖生物合成中脂连接循环的细菌易位酶。在本观点中，我们探讨了自然界如何从简单的核苷和氨基酸构建块构建复杂的肽核苷抗生素支架。我们讨论了肽核苷抗生素生物合成途径的当前研究阶段，主要集中在尿苷转化和与肽偶联的化学逻辑和酶机制上。我们进一步调查了以 pacidamycins 为代表的尿嘧啶肽抗生素的非核糖体生物合成范例，最后讨论了抗生素优化的多样化机会。
