Engineering lanthipeptides by introducing a large variety of RiPP modifications to obtain new-to-nature bioactive peptides

Yuxin Fu, Yanli Xu, Fleur Ruijne, Oscar P. Kuipers*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)
15 Downloads (Pure)

Abstract

Natural bioactive peptide discovery is a challenging and time-consuming process. However, advances in synthetic biology are providing promising new avenues in peptide engineering that allow for the design and production of a large variety of new-to-nature peptides with enhanced or new bioactivities, using known peptides as templates. Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides (RiPPs). The modularity of post-translational modification (PTM) enzymes and ribosomal biosynthesis inherent to lanthipeptides enables their engineering and screening in a high-throughput manner. The field of RiPPs research is rapidly evolving, with many novel PTMs and their associated modification enzymes being identified and characterized. The modularity presented by these diverse and promiscuous modification enzymes has made them promising tools for further in vivo engineering of lanthipeptides, allowing for the diversification of their structures and activities. In this review, we explore the diverse modifications occurring in RiPPs and discuss the potential applications and feasibility of combining various modification enzymes for lanthipeptide engineering. We highlight the prospect of lanthipeptide- and RiPP-engineering to produce and screen novel peptides, including mimics of potent non-ribosomally produced antimicrobial peptides (NRPs) such as daptomycin, vancomycin, and teixobactin, which offer high therapeutic potential.

Original languageEnglish
Article numberfuad017
Number of pages22
JournalFEMS Microbiology Reviews
Volume47
Issue number3
DOIs
Publication statusPublished - 1-May-2023

Keywords

  • Engineering
  • lanthipeptides
  • NRPs mimics
  • post-translational modification
  • ripps
  • synthetic biology

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