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类抗生素和其他聚酮肽的治疗应用:新老发现。

Therapeutic Application of Lantibiotics and Other Lanthipeptides: Old and New Findings.

机构信息

Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa.

Division of Clinical Pharmacology, Department Medicine, Stellenbosch University, Stellenbosch, South Africa.

出版信息

Appl Environ Microbiol. 2021 Jun 25;87(14):e0018621. doi: 10.1128/AEM.00186-21.

Abstract

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, with modifications that are incorporated during biosynthesis by dedicated enzymes. Various modifications of the peptides are possible, resulting in a highly diverse group of bioactive peptides that offer a potential reservoir for use in the fight against a plethora of diseases. Their activities range from the antimicrobial properties of lantibiotics, especially against antibiotic-resistant strains, to antiviral activity, immunomodulatory properties, antiallodynic effects, and the potential to alleviate cystic fibrosis symptoms. Lanthipeptide biosynthetic genes are widespread within bacterial genomes, providing a substantial repository for novel bioactive peptides. Using genome mining tools, novel bioactive lanthipeptides can be identified, and coupled with rapid screening and heterologous expression technologies, the lanthipeptide drug discovery pipeline can be significantly sped up. Lanthipeptides represent a group of bioactive peptides that hold great potential as biotherapeutics, especially at a time when novel and more effective therapies are required. With this review, we provide insight into the latest developments made toward the therapeutic applications and production of lanthipeptides, specifically looking at heterologous expression systems.

摘要

类硫霉素是一类核糖体合成和翻译后修饰的肽类,其修饰是由专门的酶在生物合成过程中掺入的。肽的各种修饰都是可能的,从而产生了高度多样化的生物活性肽群,为对抗多种疾病提供了潜在的资源。它们的活性范围从类抗生素的抗菌特性(特别是针对抗生素耐药菌株)到抗病毒活性、免疫调节特性、抗痛觉过敏作用以及缓解囊性纤维化症状的潜力。类硫霉素生物合成基因在细菌基因组中广泛存在,为新型生物活性肽提供了大量的储存库。利用基因组挖掘工具,可以鉴定新型生物活性类硫霉素,再加上快速筛选和异源表达技术,类硫霉素药物发现的管道可以大大加快。类硫霉素是一类具有生物治疗潜力的生物活性肽,尤其是在需要新型、更有效的治疗方法的时候。通过这篇综述,我们深入了解了类硫霉素在治疗应用和生产方面的最新进展,特别是在异源表达系统方面。

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