跳到正文
Nature Biotechnology·· 3 天前AI 评分27

研究发现抗生素套索肽 triculamin 生物合成需要一种不寻常的跟随肽

An unusual follower peptide is required for biosynthesis of the antibiotic lasso peptide triculamin

AI 导读

研究揭示抗生素套索肽 triculamin 的生物合成需要一种不寻常的跟随肽（follower peptide）。这一发现为套索肽类抗生素的 biosynthetic 机制提供了新线索，相关成果发表于 Nature Biotechnology。

正文 · 原文

  1. Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, et al. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep. 2012;30:108–60. https://doi.org/10.1039/C2NP20085F.

    Article  Google Scholar 

  2. Hegemann JD, Zimmermann M, Xie X, Marahiel MA. Lasso peptides: an intriguing class of bacterial natural products. Acc Chem Res. 2015;48:1909–19. https://doi.org/10.1021/acs.accounts.5b00156.

    Article  CAS  PubMed  Google Scholar 

  3. Barrett SE, Mitchell DA. Advances in lasso peptide discovery, biosynthesis, and function. Trends Genet. 2024;S0168952524001793. https://doi.org/10.1016/j.tig.2024.08.002

  4. Khatri B, Lay T, Craik DJ. Progress and challenges in the biosynthesis and chemical synthesis of lasso peptides. J Am Chem Soc. 2026;148:4777–90. https://doi.org/10.1021/jacs.5c10593.

    Article  CAS  PubMed  Google Scholar 

  5. Duan Y, Niu W, Pang L, Mu DS, Du ZJ, Zhang Y, et al. Leader peptide removal in lasso peptide biosynthesis based on penultimate isoleucine residue. Front Microbiol. 2023;14:1181125. https://doi.org/10.3389/fmicb.2023.1181125.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kretsch AM, Gadgil MG, DiCaprio AJ, Barrett SE, Kille BL, Si Y, et al. Peptidase activation by a leader peptide-bound ripp recognition element. Biochemistry. 2023;62:956–67. https://doi.org/10.1021/acs.biochem.2c00700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chekan JR, Ongpipattanakul C, Nair SK. Steric complementarity directs sequence promiscuous leader binding in RiPP biosynthesis. Proc Natl Acad Sci USA. 2019;116:24049–55. https://doi.org/10.1073/pnas.1908364116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sumida T, Dubiley S, Wilcox B, Severinov K, Tagami S. Structural basis of leader peptide recognition in lasso peptide biosynthesis pathway. ACS Chem Biol. 2019;14:1619–27. https://doi.org/10.1021/acschembio.9b00348.

    Article  CAS  PubMed  Google Scholar 

  9. Tietz JI, Schwalen CJ, Patel PS, Maxson T, Blair PM, Tai HC, et al. A new genome-mining tool redefines the lasso peptide biosynthetic landscape. Nat Chem Biol. 2017;13:470–8. https://doi.org/10.1038/nchembio.2319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Andersen FD, Pedersen KD, Wilkens Juhl D, Mygind T, Chopin P, B. Svenningsen E, et al. Triculamin: an unusual lasso peptide with potent antimycobacterial activity. J Nat Prod. 2022;85:1514–21. https://doi.org/10.1021/acs.jnatprod.2c00065.

    Article  CAS  PubMed  Google Scholar 

  11. Merrild A, Svenningsen T, Chevrette MG, Tørring T. Evolution-guided discovery of antimycobacterial triculamin-like lasso peptides. Angew Chem Int Ed. 2025;64:e202425134. https://doi.org/10.1002/anie.202425134.

    Article  CAS  Google Scholar 

  12. Suzuki S, Asahi K, Nagatsu J, Kawashima Y, Suzuki I. Triculamin, a new antituberculosis substance. J Antibiot. 1967;20:126.

    CAS  Google Scholar 

  13. Maeda K, Kondo S, Ohi K, Kondo H, Wang EL, Osato Y, et al. A new antibiotic, alboverticillin. J Antibiot. 1958;11:30–1.

    CAS  Google Scholar 

  14. Vior NM, Cea-Torrescassana E, Eyles TH, Chandra G, Truman AW. Regulation of bottromycin biosynthesis involves an internal transcriptional start site and a cluster-situated modulator. Front Microbiol. 2020;11. https://doi.org/10.3389/fmicb.2020.00495

  15. Kloosterman AM, Shelton KE, Van Wezel GP, Medema MH, Mitchell DA. RRE-Finder: a genome-mining tool for class-independent RiPP discovery. mSystems. 2020;5:e00267-20. https://doi.org/10.1128/mSystems.00267-20.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Svenningsen T, Merrild A, Wang F, Hansen FD, Johnson TG, Iwase R, et al. Biosynthesis, structure, and antibiotic properties of gelatinamin A, a triculamin-like lasso peptide. ChemBioChem. 2026;27:e70378. https://doi.org/10.1002/cbic.70378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Duquesne S, Destoumieux-Garzón D, Zirah S, Goulard C, Peduzzi J, Rebuffat S. Two enzymes catalyze the maturation of a lasso peptide in Escherichia coli. Chem Biol. 2007;14:793–803. https://doi.org/10.1016/j.chembiol.2007.06.004.

    Article  CAS  PubMed  Google Scholar 

  18. Yan K, Li Y, Zirah S, Goulard C, Knappe TA, Marahiel MA, et al. Dissecting the maturation steps of the lasso peptide microcin J25 in vitro. ChemBioChem. 2012;13:1046–52. https://doi.org/10.1002/cbic.201200016.

    Article  CAS  PubMed  Google Scholar 

  19. Cheung WL, Pan SJ, Link AJ. Much of the microcin J25 leader peptide is dispensable. J Am Chem Soc. 2010;132:2514–5. https://doi.org/10.1021/ja910191u.

    Article  CAS  PubMed  Google Scholar 

  20. Koos JD, Link AJ. Heterologous and in vitro reconstitution of fuscanodin, a lasso peptide from Thermobifida fusca. J Am Chem Soc. 2019;141:928–35. https://doi.org/10.1021/jacs.8b10724.

    Article  CAS  PubMed  Google Scholar 

  21. DiCaprio AJ, Firouzbakht A, Hudson GA, Mitchell DA. Enzymatic reconstitution and biosynthetic investigation of the lasso peptide fusilassin. J Am Chem Soc. 2019;141:290–7. https://doi.org/10.1021/jacs.8b09928.

    Article  CAS  PubMed  Google Scholar 

  22. Zyubko T, Serebryakova M, Andreeva J, Metelev M, Lippens G, Dubiley S, et al. Efficient in vivo synthesis of lasso peptide pseudomycoidin proceeds in the absence of both the leader and the leader peptidase. Chem Sci. 2019;10:9699–707. https://doi.org/10.1039/c9sc02370d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Abramson J, Adler J, Dunger J, Evans R, Green T, Pritzel A, et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature. 2024;630:493–500. https://doi.org/10.1038/s41586-024-07487-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Oman TJ, van der Donk WA. Follow the leader: the use of leader peptides to guide natural product biosynthesis. Nat Chem Biol. 2010;6:9–18. https://doi.org/10.1038/nchembio.286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jangra M, Travin DY, Kaur M, Hackenberger D, Koteva K, Polikanov YS, et al. An acetyltransferase conferring self-resistance of the producer to lasso peptide antibiotic lariocidin. ACS Infect Dis. 2026;12:714–23. https://doi.org/10.1021/acsinfecdis.5c00885.

    Article  CAS  PubMed  Google Scholar 

  26. Jangra M, Travin DY, Aleksandrova EV, Kaur M, Darwish L, Koteva K, et al. A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome. Nature. 2025;640:1022–30. https://doi.org/10.1038/s41586-025-08723-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kunakom S, Eustáquio AS. Heterologous production of lasso peptide capistruin in a Burkholderia host. ACS Synth Biol. 2020;9:241–8. https://doi.org/10.1021/acssynbio.9b00438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fernandez HN, Kretsch AM, Kunakom S, Kadjo AE, Mitchell DA, Eustáquio AS. High-yield lasso peptide production in a Burkholderia bacterial host by plasmid copy number engineering. ACS Synth Biol. 2024;13:337–50. https://doi.org/10.1021/acssynbio.3c00597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Brademan DR, Riley NM, Kwiecien NW, Coon JJ. Interactive peptide spectral annotator: a versatile web-based tool for proteomic applications. Mol Cell Proteom. 2019;18:S193–201. https://doi.org/10.1074/mcp.TIR118.001209.

    Article  CAS  Google Scholar 

来源：Nature Biotechnology · nature.com

技术平台研发与科学#研发/科学#创新药#小分子

AI 摘要声明：站内标题、摘要与推荐理由由模型基于公开来源生成，属机器生成内容，非原文；本页内容仅供医药行业信息参考，不构成医疗建议、诊断或用药依据。