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Discovery and characterization of a novel C-terminal peptide carboxyl methyltransferase in a lassomycin-like lasso peptide biosynthetic pathway

  • Yu Su
  • Meng Han
  • Xianbin Meng
  • Yue Feng
  • Shizhong Luo
  • Changyuan Yu
  • Guojun ZhengEmail author
  • Shaozhou ZhuEmail author
Biotechnologically relevant enzymes and proteins
  • 107 Downloads

Abstract

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.

Keywords

Lasso peptide Lassomycin Methyltransferase Ribosomally synthesized and post-translationally modified peptides 

Notes

Funding information

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.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors

Supplementary material

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ESM 1 (PDF 2547 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Chemical Resources EngineeringBeijing University of Chemical TechnologyBeijingPeople’s Republic of China
  2. 2.College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingPeople’s Republic of China
  3. 3.MOE Key Laboratory of Bioinformatics, School of Life SciencesTsinghua UniversityBeijingPeople’s Republic of China

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