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羊毛硫抗生素:结构与功能多样的肽类

Lantibiotics: peptides of diverse structure and function.

作者信息

Willey Joanne M, van der Donk Wilfred A

机构信息

Department of Biology, Hofstra University, Hempstead, New York 11549, USA.

出版信息

Annu Rev Microbiol. 2007;61:477-501. doi: 10.1146/annurev.micro.61.080706.093501.

Abstract

The current need for antibiotics with novel target molecules has coincided with advances in technical approaches for the structural and functional analysis of the lantibiotics, which are ribosomally synthesized peptides produced by gram-positive bacteria. These peptides have antibiotic or morphogenetic activity and are structurally defined by the presence of unusual amino acids introduced by posttranslational modification. Lantibiotics are complex polycyclic molecules formed by the dehydration of select Ser and Thr residues and the intramolecular addition of Cys thiols to the resulting unsaturated amino acids to form lanthionine and methyllanthionine bridges, respectively. Importantly, the structural and functional diversity of the lantibiotics is much broader than previously imagined. Here we discuss this growing collection of molecules and introduce some recently discovered peptides, review advances in enzymology and protein engineering, and discuss the regulatory networks that govern the synthesis of the lantibiotics by the producing organisms.

摘要

当前对具有新型靶标分子的抗生素的需求,与羊毛硫抗生素结构和功能分析技术方法的进展相契合,羊毛硫抗生素是革兰氏阳性菌产生的核糖体合成肽。这些肽具有抗生素或形态发生活性,其结构由翻译后修饰引入的不寻常氨基酸决定。羊毛硫抗生素是由特定丝氨酸和苏氨酸残基脱水以及分子内半胱氨酸硫醇加成到所得不饱和氨基酸上分别形成羊毛硫氨酸和甲基羊毛硫氨酸桥而形成的复杂多环分子。重要的是,羊毛硫抗生素的结构和功能多样性比以前想象的要广泛得多。在这里,我们讨论这一不断增加的分子集合,介绍一些最近发现的肽,回顾酶学和蛋白质工程方面的进展,并讨论控制产生菌合成羊毛硫抗生素的调控网络。

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