Discovery and characterization of a novel C-terminal peptide carboxyl methyltransferase in a lassomycin-like lasso peptide biosynthetic pathway
- 525 Downloads
Lasso peptides belong to a peculiar family of ribosomally synthesized and post-translationally modified peptides (RiPPs)—natural products with an unusual isopeptide-bonded slipknot structure. Except for assembling of this unusual lasso fold, several further post-translational modifications of lasso peptides, including C-terminal methylation, phosphorylation/poly-phosphorylation, citrullination, and acetylation, have been reported recently. However, most of their biosynthetic logic have not been elucidated except the phosphorylated paeninodin lasso peptide. Herein, we identified two novel lassomycin-like lasso peptide biosynthetic pathways and, for the first time, characterized a novel C-terminal peptide carboxyl methyltransferase involved in these pathways. Our investigations revealed that this new family of methyltransferase could specifically methylate the C terminus of precursor peptide substrates, eventually leading to lassomycin-like C-terminal methylated lasso peptides. Our studies offer another rare insight into the extraordinary strategies of chemical diversification adopted by lasso peptide biosynthetic machinery and predicated two valuable sources for methylated lasso peptide discovery.
KeywordsLasso peptide Lassomycin Methyltransferase Ribosomally synthesized and post-translationally modified peptides
This work was supported by the Fundamental Research Funds for the Central Universities (No. XK1802-8 and XK1803-06), National Natural Science Foundation of China (NSFC, Grant No. 21706005), and National Great Science and Technology Projects (2018ZX09721001).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors
- Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD, Craik DJ, Dawson M, Dittmann E, Donadio S, Dorrestein PC, Entian K-D, Fischbach MA, Garavelli JS, Goransson U, Gruber CW, Haft DH, Hemscheidt TK, Hertweck C, Hill C, Horswill AR, Jaspars M, Kelly WL, Klinman JP, Kuipers OP, Link AJ, Liu W, Marahiel MA, Mitchell DA, Moll GN, Moore BS, Muller R, Nair SK, Nes IF, Norris GE, Olivera BM, Onaka H, Patchett ML, Piel J, Reaney MJT, Rebuffat S, Ross RP, Sahl H-G, Schmidt EW, Selsted ME, Severinov K, Shen B, Sivonen K, Smith L, Stein T, Sussmuth RD, Tagg JR, Tang G-L, Truman AW, Vederas JC, Walsh CT, Walton JD, Wenzel SC, Willey JM, van der Donk WA (2013) Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 30(1):108–160. https://doi.org/10.1039/C2NP20085F CrossRefPubMedPubMedCentralGoogle Scholar
- Cano-Muniz S, Anthony R, Niemann S, Alffenaar JC (2018) New approaches and therapeutic options for Mycobacterium tuberculosis in a dormant state. Clin Microbiol Rev 31(1). https://doi.org/10.1128/CMR.00060-17
- Elsayed SS, Trusch F, Deng H, Raab A, Prokes I, Busarakam K, Asenjo JA, Andrews BA, van West P, Bull AT, Goodfellow M, Yi Y, Ebel R, Jaspars M, Rateb ME (2015) Chaxapeptin, a lasso peptide from Extremotolerant Streptomyces leeuwenhoekii strain C58 from the Hyperarid Atacama Desert. J Org Chem 80(20):10252–10260. https://doi.org/10.1021/acs.joc.5b01878 CrossRefPubMedGoogle Scholar
- Gavrish E, Sit Clarissa S, Cao S, Kandror O, Spoering A, Peoples A, Ling L, Fetterman A, Hughes D, Bissell A, Torrey H, Akopian T, Mueller A, Epstein S, Goldberg A, Clardy J, Lewis K (2014) Lassomycin, a Ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. Chem Biol 21(4):509–518. https://doi.org/10.1016/j.chembiol.2014.01.014 CrossRefPubMedPubMedCentralGoogle Scholar
- Knappe TA, Linne U, Zirah S, Rebuffat S, Xie X, Marahiel MA (2008) Isolation and structural characterization of capistruin, a lasso peptide predicted from the genome sequence of Burkholderia thailandensis E264. J Am Chem Soc 130(34):11446–11454. https://doi.org/10.1021/ja802966g CrossRefPubMedGoogle Scholar
- Li Y, Ducasse R, Zirah S, Blond A, Goulard C, Lescop E, Giraud C, Hartke A, Guittet E, Pernodet J-L, Rebuffat S (2015) Characterization of Sviceucin from Streptomyces provides insight into enzyme exchangeability and disulfide bond formation in lasso peptides. ACS Chem Biol 10(11):2641–2649. https://doi.org/10.1021/acschembio.5b00584 CrossRefPubMedGoogle Scholar
- Mahanta N, Zhang Z, Hudson GA, van der Donk WA, Mitchell DA (2017) Reconstitution and substrate specificity of the radical S-Adenosyl-methionine Thiazole C-methyltransferase in Thiomuracin biosynthesis. J Am Chem Soc 139(12):4310–4313. https://doi.org/10.1021/jacs.7b00693 CrossRefPubMedPubMedCentralGoogle Scholar
- Metelev M, Tietz Jonathan I, Melby Joel O, Blair Patricia M, Zhu L, Livnat I, Severinov K, Mitchell Douglas A (2015) Structure, bioactivity, and resistance mechanism of Streptomonomicin, an unusual lasso peptide from an understudied halophilic Actinomycete. Chem Biol 22(2):241–250. https://doi.org/10.1016/j.chembiol.2014.11.017 CrossRefPubMedPubMedCentralGoogle Scholar
- Metelev M, Arseniev A, Bushin LB, Kuznedelov K, Artamonova TO, Kondratenko R, Khodorkovskii M, Seyedsayamdost MR, Severinov K (2017) Acinetodin and Klebsidin, RNA polymerase targeting lasso peptides produced by human isolates of Acinetobacter gyllenbergii and Klebsiella pneumoniae. ACS Chem Biol 12(3):814–824. https://doi.org/10.1021/acschembio.6b01154 CrossRefPubMedGoogle Scholar
- Mevaere J, Goulard C, Schneider O, Sekurova ON, Ma H, Zirah S, Afonso C, Rebuffat S, Zotchev SB, Li Y (2018) An orthogonal system for heterologous expression of actinobacterial lasso peptides in Streptomyces hosts. Sci Rep 8(1):8232. https://doi.org/10.1038/s41598-018-26620-0 CrossRefPubMedPubMedCentralGoogle Scholar
- Ogawa T, Ochiai K, Tanaka T, Tsukuda E, Chiba S, Yano K, Yamasaki M, Yoshida M, Matsuda Y (1995) RES-701-2, −3 and −4, novel and selective endothelin type B receptor antagonists produced by Streptomyces sp. I. Taxonomy of producing strains, fermentation, isolation, and biochemical properties. J Antibiot 48(11):1213–1220CrossRefGoogle Scholar
- Wu B, Wijma HJ, Song L, Rozeboom HJ, Poloni C, Tian Y, Arif MI, Nuijens T, Quaedflieg PJLM, Szymanski W, Feringa BL, Janssen DB (2016) Versatile peptide C-terminal functionalization via a computationally engineered peptide amidase. ACS Catal 6(8):5405–5414. https://doi.org/10.1021/acscatal.6b01062 CrossRefGoogle Scholar