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Functional Genome Mining Reveals a Class V Lanthipeptide Containing a d-Amino Acid Introduced by an F420 H2 -Dependent Reductase.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-07-09 , DOI: 10.1002/anie.202008035
Min Xu 1 , Fei Zhang 1 , Zhuo Cheng 1 , Ghader Bashiri 2 , Jing Wang 1 , Jiali Hong 1 , Yemin Wang 1 , Lijun Xu 1 , Xuefei Chen 1 , Sheng-Xiong Huang 3 , Shuangjun Lin 1 , Zixin Deng 1 , Meifeng Tao 1
Affiliation  

Lantibiotics are a type of ribosomally synthesized and post‐translationally modified peptides (termed lanthipeptides) with often potent antimicrobial activity. Herein, we report the discovery of a new lantibiotic, lexapeptide, using the library expression analysis system (LEXAS) approach. Lexapeptide has rare structural modifications, including N‐terminal (N,N)‐dimethyl phenylalanine, C‐terminal (2‐aminovinyl)‐3‐methyl‐cysteine, and d‐Ala. The characteristic lanthionine moiety in lexapeptide is formed by three proteins (LxmK, LxmX, and LxmY), which are distinct from enzymes known to be involved in lanthipeptide biosynthesis. Furthermore, a novel F420H2‐dependent reductase (LxmJ) from the lexapeptide biosynthetic gene cluster (BGC) is identified to catalyze the reduction of dehydroalanine to install d‐Ala. Our findings suggest that lexapeptide is the founding member of a new class of lanthipeptides that we designate as class V. We also identified further class V lanthipeptide BGCs in actinomycetes and cyanobacteria genomes, implying that other class V lantibiotics await discovery.

中文翻译:

功能基因组采矿揭示了包含由F420 H2依赖性还原酶引入的d-氨基酸的V类Lanthepteptide。

羊毛硫抗生素是一种核糖体合成和翻译后修饰的肽(称为lanthipepteptides),通常具有很强的抗菌活性。本文中,我们报告了使用文库表达分析系统(LEXAS)方法发现的新羊毛硫抗生素lexapeptide。Lexapeptide具有罕见的结构修饰,包括N端(NN)-二甲基苯丙氨酸,C端(2-氨基乙烯基)-3-甲基半胱氨酸和d -Ala 。lexapeptide中的特征性羊毛硫氨酸部分是由三种蛋白质(LxmK,LxmX和LxmY)形成的,这三种蛋白质与已知参与多肽肽生物合成的酶截然不同。此外,新型F 420 H 2lexapeptide生物合成基因簇(BGC)中的依赖依赖性还原酶(LxmJ)可催化脱氢丙氨酸的还原并安装d -Ala。我们的发现表明,lexapeptide是我们指定为V类的一类新的脂肽的创始成员。我们还在放线菌和蓝细菌基因组中进一步鉴定了V类脂肽BGC,这暗示着其他V类lantibiotics尚待发现。
更新日期:2020-07-09
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