合成生物学指导下芽孢杆菌合成环脂肽的研究进展*

近年来,合成生物学借助工程化在人工生命系统的设计与构建方面取得了长足进展,特别是“细胞工厂”的开发和应用为天然产物的合成带来了深刻变革。环脂肽是一类新型的天然表面活性剂,因其特殊的结构和功能亦可作为抗生素使用。目前,合成环脂肽最理想的微生物底盘是芽孢杆菌。因此,许多研究者致力于通过合成生物学技术来提升芽孢杆菌作为环脂肽细胞工厂的性能。首先,对芽孢杆菌中环脂肽的非核糖体肽合成途径进行概述;其次,重点介绍与环脂肽合成相关的调控因子;再次,从底盘细胞的选择、基因编辑工具的开发、合成路径的优化及发酵过程的优化等四个方面对合成生物学指导下环脂肽的相关研究进展进行总结;最后,讨论环脂肽合成中可能存在的挑战,并就未来研究趋势进行展望,以期为高效环脂肽细胞工厂的开发提供参考。

Research Progress of Cyclic Lipopeptides Synthesized by Bacillus under the Guidance of Synthetic Biology

In recent years, synthetic biology has made great progress in the design and construction of artificial life systems with the help of engineering ideas. In particular, the development and application of “cell factories” have brought profound changes to the synthesis of natural products. Cyclic lipopeptides are new natural surfactants. They can also be used as antibiotics because of their special structures and functions. At present, Bacillus are the most ideal microbial chassis for cyclic lipopeptides synthesis. Therefore, many researchers are devoted to improving the performance of Bacillus as cyclic lipopeptides cell factories through synthetic biology techniques. In this paper, the non-ribosomal peptide synthesis pathway of cyclic lipopeptides synthesized by Bacillus is first reviewed. Second, the regulatory factors related to the synthesis of cyclic lipopeptides are introduced. Third, the research progress of cyclic lipopeptides synthesis under the guidance of synthetic biology are summarized from the aspects including the selection of chassis cells, the development of gene editing tools, the optimization of synthesis pathway and the optimization of fermentation process. Finally, the possible challenges in cyclic lipopeptides synthesis are discussed and the future research trends are prospected. These will provide reference for the development of efficient cyclic lipopeptides cell factories.