Yanqing Xue, Yijiao Xiong, Wei Huang, Jianing Liu, Wen Liu
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引用次数: 0
摘要
得益于基因组挖掘的最新进展,核糖体合成和翻译后修饰肽(RiPP)天然产物已经成为化学灵感的来源,推动了治疗药物的发现和新生物工具的开发,以应对合成方法的挑战。尽管局限于20个蛋白质原氨基酸构建块,但由酶促翻译后修饰(PTMs)产生的RiPPs的结构复杂性和多样性超出了预期,现在被认为与非核糖体肽合成酶产生的RiPPs相当。在这里,我们重点介绍了在过去十年中表征的PTM酶,这些酶在转化中参与-(nh - c - α- co)n-重复单元,特别是那些通过肽骨架重塑导致结构重排的酶。揭示这些不寻常的PTM酶的催化机制加深了对RiPP生物合成的理解,最终将提高我们利用合成生物学策略合理设计、开发和生产功能肽制剂的能力。
Remodeling of ribosomally synthesized peptide backbones based on posttranslational modifications.
Covering: 2013-2024Benefiting significantly from recent advances in genome mining, ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products have emerged as a source of chemical inspiration to drive the discovery of therapeutic agents and the development of new biological tools for addressing challenges to synthetic approaches. Despite being confined to twenty proteinogenic amino acid building blocks, the structural complexity and diversity of RiPPs that arise from enzymatic posttranslational modifications (PTMs) surpass expectations and are now believed to be comparable to those produced by non-ribosomal peptide synthetases. Here, we highlight the PTM enzymes characterized over the past decade that engage the -(NH-Cα-CO)n- repeating units in transformations, particularly those leading to structural rearrangements by peptide backbone remodeling. Unveiling the catalytic mechanisms of these unusual PTM enzymes deepens the understanding in RiPP biosynthesis and, eventually, will enhance our capability of rational design, development and production of functional peptide agents using synthetic biology strategies.
期刊介绍:
Natural Product Reports (NPR) serves as a pivotal critical review journal propelling advancements in all facets of natural products research, encompassing isolation, structural and stereochemical determination, biosynthesis, biological activity, and synthesis.
With a broad scope, NPR extends its influence into the wider bioinorganic, bioorganic, and chemical biology communities. Covering areas such as enzymology, nucleic acids, genetics, chemical ecology, carbohydrates, primary and secondary metabolism, and analytical techniques, the journal provides insightful articles focusing on key developments shaping the field, rather than offering exhaustive overviews of all results.
NPR encourages authors to infuse their perspectives on developments, trends, and future directions, fostering a dynamic exchange of ideas within the natural products research community.