Abstract
Lasso peptides are ribosomally synthesized and post-translationally modified natural products with a characteristic slipknot-like structure, which confers these peptides remarkable stability and diverse pharmacologically relevant bioactivities. Among all the reported lasso peptides, lassomycin and lariatins are unique lasso peptides that exhibit noticeable anti-tuberculosis (TB) activity. Due to the unique threaded structure and the unusual bactericidal mechanism toward Mycobacterium tuberculosis, these peptides have drawn considerable interest, not only in the field of total synthesis but also in several other fields including biosynthesis, bioengineering, and structure-activity studies. During the past few years, significant progress has been made in understanding the biosynthetic mechanism of these intriguing compounds, which has provided a solid foundation for future work. This review highlights recent achievements in the discovery, structure elucidation, biological activity, and the unique anti-TB mechanism of lasso peptides. Moreover, the discovery of their biosynthetic pathway has laid the foundation for combinatorial biosynthesis of their analogs, which provides new perspectives for the production of novel anti-TB lasso peptides.
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This work was supported by the Fundamental Research Funds for the Central Universities (XK1802-8 and XK1803-06), National Natural Science Foundation of China (NSFC, Grant No. 21706005), and National Great Science and Technology Projects (2018ZX09721001). Dedicated to Renzhi Zhu.
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Zhu, S., Su, Y., Shams, S. et al. Lassomycin and lariatin lasso peptides as suitable antibiotics for combating mycobacterial infections: current state of biosynthesis and perspectives for production. Appl Microbiol Biotechnol 103, 3931–3940 (2019). https://doi.org/10.1007/s00253-019-09771-6
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DOI: https://doi.org/10.1007/s00253-019-09771-6