Centro de Análises Proteômicas e Bioquímicas, Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília , Brasília, Brazil.
Universidade de Brasília, Pós-graduação em Patologia Molecular, Campus Darcy Ribeiro , Brasília, Brazil.
Expert Rev Clin Pharmacol. 2020 Apr;13(4):367-390. doi: 10.1080/17512433.2020.1764347. Epub 2020 Jun 16.
The need to develop new drugs for the control of pathogenic microorganisms has redoubled efforts to prospect for antimicrobial peptides (AMPs) from natural sources and to characterize its structure and function. These molecules present a broad spectrum of action against different microorganisms and frequently present promiscuous action, with anticancer and immunomodulatory activities. Furthermore, AMPs can be used as biopharmaceuticals in the treatment of hospital-acquired infections and other serious diseases with relevant social and economic impacts.: The low yield and the therefore difficult extraction and purification process in AMPs are problems that limit their industrial application and scientific research. Thus, optimized heterologous expression systems were developed to significantly boost AMP yields, allow high efficiency in purification and structural optimization for the increase of therapeutic activity.: This review provides an update on recent developments in the recombinant production of ribosomal and non-ribosomal synthesis of AMPs and on strategies to increase the expression of genes encoding AMPs at the transcriptional and translational levels and regulation of the post-translational modifications. Moreover, there are detailed reports of AMPs that have already reached marketable status or are in the pipeline under advanced stages of preclinical testing.
为了控制病原微生物,开发新药的需求促使人们加倍努力,从天然来源中寻找抗菌肽 (AMPs),并对其结构和功能进行表征。这些分子对不同的微生物具有广谱的作用,并且经常具有混杂的作用,具有抗癌和免疫调节活性。此外,AMPs 可以用作治疗医院获得性感染和其他严重疾病的生物制药,具有相关的社会和经济影响。AMP 的产量低,因此提取和纯化过程困难,这是限制其工业应用和科学研究的问题。因此,开发了优化的异源表达系统,以显著提高 AMP 的产量,允许高效纯化和结构优化,以提高治疗活性。
本综述提供了有关核糖体和非核糖体合成 AMP 的重组生产的最新进展,以及在转录和翻译水平上增加编码 AMP 的基因表达和调节翻译后修饰的策略的最新进展。此外,还有详细的报告介绍了已经达到可销售状态或处于临床前测试的高级阶段的 AMP。