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近年来大规模重组生产抗菌肽的成就与展望。

Recent achievements and perspectives for large-scale recombinant production of antimicrobial peptides.

机构信息

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, 4072, Australia.

Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD, 4111, Australia.

出版信息

Appl Microbiol Biotechnol. 2019 Jan;103(2):659-671. doi: 10.1007/s00253-018-9524-1. Epub 2018 Nov 23.

Abstract

Antibiotic resistance poses a growing threat to global public health. It is urgent to develop new alternative antibiotics. Antimicrobial peptide (AMP) is a diverse class of natural-occurring molecules that constitute immune systems of living organisms. More than 2500 AMPs have been identified and isolated from natural sources. Compared to conventional antibiotics, AMPs exhibit antimicrobial activities against a broad spectrum of microorganisms including bacteria, fungi, and even viruses. More importantly, the unique antimicrobial mechanisms of AMPs make it difficult for microorganisms to develop resistance. Therefore, it is very promising to develop AMPs as high-value antimicrobial candidates. This mini review provides an update of recent progresses in recombinant production of AMPs after fusion of AMP with carrier proteins and their scale-up. Key factors including selection of expression host and fusion tags are firstly introduced, followed by subsequent discussions on purification of fusion proteins and recovery of antimicrobial peptides. The scale production of AMPs is also explored.

摘要

抗生素耐药性对全球公共健康构成日益严重的威胁。开发新的替代抗生素迫在眉睫。抗菌肽(Antimicrobial Peptide,AMP)是一类广泛存在的天然分子,构成了生物体的免疫系统。已经从天然来源中鉴定和分离出超过 2500 种 AMP。与传统抗生素相比,AMP 对包括细菌、真菌甚至病毒在内的广谱微生物具有抗菌活性。更重要的是,AMP 的独特抗菌机制使得微生物难以产生耐药性。因此,将 AMP 开发为高价值的抗菌候选药物具有广阔的前景。本综述简要介绍了 AMP 与载体蛋白融合后的重组生产及其放大规模的最新进展。首先介绍了表达宿主和融合标签的选择等关键因素,随后讨论了融合蛋白的纯化和抗菌肽的回收。还探讨了 AMP 的规模化生产。

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