环脂肽生物合成的研究进展

doi:10.12211/2096-8280.2021-008

摘要/Abstract

摘要：

环脂肽化合物是一类结构新颖的环状肽类，其两亲性的物化特性决定了其独特的生物活性，可作为抗生素、生物表面活性剂等。在生物防治、药物开发、环境修复和疾病治疗等方面广泛应用，具有迫切的市场需求和广阔的发展前景。环脂肽类天然产物主要由非核糖体肽合成途径合成，由于环脂肽合成复杂的代谢网络和前体需求、专一且严格的合成途径、多种同系物的共存，制约着环脂肽合成的微生物开发和产品价值提升。本文主要介绍了来源于细菌界的环脂肽类物质的结构特性，非核糖体肽合成途径及非核糖体肽合成酶（non-ribosomal peptide synthetase，NRPS）的结构域特点，天然产物底盘菌株开发现状，通过基因工程、代谢工程方法进行同系物调控和生物合成策略，混菌对脂肽生物合成的影响，以及合成生物学在脂肽合成中的应用。随着合成生物技术的迅速发展和运用，环脂肽类天然产物的微生物合成也有望实现“质”和“量”的提升，以及促进新型脂肽的开发。

关键词: 环脂肽, 非核糖体肽合成途径, NRPS, 模块结构域, 同系物调控, 合成生物学

Abstract:

As antibiotics and bio-surfactants,cyclic lipopeptides have unique molecular structure and biological activity and are widely applied in the fields of biological control, drug development, environmental remediation and disease treatment. It has vigorous market demand and promising future. Cyclic lipopeptides are a class of antibiotics synthesized from non-ribosomal peptide pathways by microorganisms. However, the complex metabolic network and precursor requirements, specific and strict synthetic pathway, and the coexistence of multiple homologues are restricting our capability of developing the lipopeptide syntheses potential of microorganism and promoting the product value of lipopeptide of bacteria. In this paper, we summarize the types of chassis cells for producing cyclic lipopeptides. We also introduce the structural characteristics of cyclic lipopeptides based on bacterial origin, synthesis pathway of non-ribosomal peptide, and structural domain characteristics of non-ribosomal peptide synthetase. In addition, the strategies for homologues regulation and biosynthetic yield improvement through genetic and metabolic engineering methods were reviewed, as well as the development status of natural product chassis strains. The synthesis of lipopeptide products can be effectively improved by optimizing the precursor metabolism, enhancing the expression of lipopeptide synthesis gene cluster, blocking the competitive pathway of lipopeptide synthesis, and the modification of various regulatory factors. The non-ribosomal peptide synthetase structural domain can be modified to obtain higher value lipopeptide and new lipopeptide drugs. We also review the effects of mixed-culture on lipopeptide syntheses, the development status of chassis strains for producing natural product, and the application of synthetic biology for improving lipopeptide biosynthesis. With the rapid development and application of synthetic biotechnology, the quality and quantity of natural lipopeptide from microorganisms will be improved rapidly. It also boosts the development of novel cyclic lipopeptides. And a better understanding of the synthesis, modification and mechanism of action of antimicrobial peptides will restart its commercial development.

Key words: cyclic lipopeptide, non-ribosomal peptide synthesis pathway, NRPS, module domain, homologous regulation, synthetic biology

中图分类号:

Q815

侯正杰, 孙慧中, 白松, 陈新月, 曹春阳, 程景胜. 环脂肽生物合成的研究进展[J]. 合成生物学, 2021, 2(4): 577-597.

Zhengjie HOU, Huizhong SUN, Song BAI, Xinyue CHEN, Chunyang CAO, Jingsheng CHENG. Research progress of cyclic lipopeptide biosynthesis[J]. Synthetic Biology Journal, 2021, 2(4): 577-597.

图/表 19

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