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扩展遗传密码用于工程化核糖体合成和翻译后修饰的肽天然产物(RiPPs)。

Expanded genetic code for the engineering of ribosomally synthetized and post-translationally modified peptide natural products (RiPPs).

机构信息

Technische Universität Berlin (Berlin Institute of Technology), Department of Chemistry, Biocatalysis Group, Müller-Breslau-Straße 10, D-10623 Berlin, Germany.

出版信息

Curr Opin Biotechnol. 2013 Aug;24(4):591-8. doi: 10.1016/j.copbio.2013.02.026. Epub 2013 Mar 25.

DOI:10.1016/j.copbio.2013.02.026
PMID:23537814
Abstract

The number of constituent amino acids in ribosomally synthetized and post-translationally modified peptide natural products (RiPPs) is restricted to the 20 canonical amino acids. Microorganisms with an engineered genetic code are capable of delivering the biological, chemical, or physical properties of many unnatural or synthetic noncanonical amino acids, ncAAs (in different combinations of their numbers and chemistry) precisely defined by the chemist at the bench. In this way, post-translational modifications (PTMs) which make RiPPs chemically extremely rich can be augmented by the co-translational insertion of ncAAs. This will dramatically expand the chemical and functional space of these molecules and enable the design of novel and unique sequence combinations with improved specificity, stability, membrane permeability and even better oral availability.

摘要

核糖体合成和翻译后修饰的肽天然产物(RiPPs)的组成氨基酸数量受限于 20 种常见氨基酸。经过基因工程改造的微生物能够提供许多非天然或合成的非标准氨基酸(ncAAs)的生物、化学或物理特性,这些特性由实验室中的化学家以不同的数量和化学组合精确定义。通过这种方式,可以通过共翻译插入 ncAAs 来修饰 RiPPs,从而增加翻译后修饰(PTMs)的化学多样性。这将极大地扩展这些分子的化学和功能空间,并能够设计具有改进的特异性、稳定性、膜通透性甚至更好的口服生物利用度的新型独特序列组合。

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