Engineering of new-to-nature ribosomally synthesized and post-translationally modified peptide natural products.

Engineering of new-to-nature ribosomally synthesized and post-translationally modified peptide natural products.
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天然核糖体合成及翻译后修饰肽天然产物工程。

DOI:
10.1016/j.copbio.2020.12.022
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发表时间:
2021-06
影响因子:
7.7
通讯作者:
van der Donk WA
van der Donk WA
中科院分区:
工程技术1区
文献类型:
--
作者:
Wu C;van der Donk WA

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天然产品历来是药物开发的重要主要来源,特别是在抗击传染病方面。越来越多地,它们的结构复杂的支架也被设想为它们没有进化的应用的领头羊,这是一种通过工程设计新的自然类比的方法。核糖体合成和翻译后修饰多肽(Ripps)是一种很有前途的生物工程候选材料,因为它们是基因编码的,其生物合成酶具有显著的底物耐受性。这篇综述重点介绍了通过基因组挖掘发现高度不寻常的新反应以及应用工程方法产生和筛选新的RIPP变异体的最新进展。此外,通过使用合成生物学方法,已发现具有增强或全新活性的杂化分子,这为RIPPS作为潜在的下一代疗法的未来发展打开了大门。
Natural products have historically been important lead sources for drug development, particularly to combat infectious diseases. Increasingly, their structurally complex scaffolds are also envisioned as leads for applications for which they did not evolve, an approach aided by engineering of new-to-nature analogs. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are promising candidates for bioengineering because they are genetically encoded and their biosynthetic enzymes display significant substrate tolerance. This review highlights recent advances in the discovery of highly unusual new reactions by genome mining and the application of engineering approaches to generate and screen novel RiPP variants. Furthermore, through the use of synthetic biology approaches, hybrid molecules with enhanced or completely new activities have been identified, which opens the door for future advancement of RiPPs as potential next-generation therapeutics.
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发表时间: 2020-09
期刊: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
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