Nonribosomal peptide synthetase biosynthetic clusters of ESKAPE pathogens.
Nonribosomal peptide synthetase biosynthetic clusters of ESKAPE pathogens.
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DOI：
10.1039/c7np00029d
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发表时间：
2017-08-02
影响因子：
11.9
通讯作者：
Gulick AM
中科院分区：
文献类型：
--
作者：
Gulick AM
天然产物是由细菌和真菌产生的重要次级代谢产物，在细胞生长和信号传导、营养获取、种内和种间通信以及毒力中发挥重要作用。天然产物的一个子集是由非核糖体肽合成酶（NRPS）产生的，NRPS是一个以装配线方式发挥功能的大型模块化酶家族。由于许多NRPS产品的药物活性，许多努力都投入到探索其生物合成途径和它们制造的不同产品中。许多有趣的NRPS途径已被确定和表征，从陆地和海洋细菌来源。最近，已经鉴定了人类肠道细菌物种中的几种NRPS途径，其产生具有抗生素活性的分子，这表明感兴趣的NRPS途径的另一个来源可能是生活在人体上的肠道细菌和致病细菌。ESKAPE病原体（屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属）已被确定为人类细菌感染的重要原因，这些细菌感染通常具有多药耐药性。这些微生物的耐药性特征促使多个国际机构呼吁确定新的抗菌靶标，并开发新的方法来治疗ESKAPE病原体的感染。这些物种中的每一个都包含几个NRPS生物合成基因簇。虽然有些已经得到很好的表征，并产生已知的天然产物，在微生物生理学中具有重要的生物学作用，但其他的还有待研究。本文综述了ESKAPE病原体的NRPS途径。新的NRPS产品的探索可能会导致更好地了解人类病原体所使用的化学通讯，并可能发现新的治疗方法。本文综述了ESKAPE病原菌NRPS生物合成基因簇产生的肽类天然产物
Natural products are important secondary metabolites produced by bacterial and fungal species that play important roles in cellular growth and signaling, nutrient acquisition, intra- and interspecies communication, and virulence. A subset of natural products is produced by nonribosomal peptide synthetases (NRPSs), a family of large, modular enzymes that function in an assembly line fashion. Because of the pharmaceutical activity of many NRPS products, much effort has gone into the exploration of their biosynthetic pathways and the diverse products they make. Many interesting NRPS pathways have been identified and characterized from both terrestrial and marine bacterial sources. Recently, several NRPS pathways in human commensal bacterial species have been identified that produce molecules with antibiotic activity, suggesting another source of interesting NRPS pathways may be the commensal and pathogenic bacteria that live on the human body. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) have been identified as a significant cause of human bacterial infections that are frequently multidrug resistant. The emerging resistance profile of these organisms has prompted calls from multiple international agencies to identify novel antibacterial targets and develop new approaches to treat infections from ESKAPE pathogens. Each of these species contains several NRPS biosynthetic gene clusters. While some have been well characterized and produce known natural products with important biological roles in microbial physiology, others have yet to be investigated. This review catalogs the NRPS pathways of ESKAPE pathogens. The exploration of novel NRPS products may lead to a better understanding of the chemical communication used by human pathogens and potentially to the discovery of novel therapeutic approaches. This review describes the peptide natural products produced by NRPS biosynthetic gene clusters from the ESKAPE pathogens
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