Engineering ribosomally synthesized and posttranslationally modified peptides as new antibiotics

• Published in: Current opinion in biotechnology 2023-04, Vol.80, p.102891-102891, Article 102891
• Main Author: Vagstad, Anna L
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Biological Products - metabolism; Peptides - chemistry; Protein Processing, Post-Translational
• ISSN: 0958-1669; 1879-0429
• DOI: 10.1016/j.copbio.2023.102891

The rise of antimicrobial resistance is an urgent public health threat demanding the invention of new drugs to combat infections. Naturally sourced nonribosomal peptides (NRPs) have a long history as antimicrobial drugs. Through recent advances in genome mining and engineering technologies, their ribosomally synthesized and posttranslationally modified peptide (RiPP) counterparts are poised to further contribute to the arsenal of anti-infectives. As natural products from diverse organisms involved in interspecies competition, many RiPPs already possess antimicrobial activities that can be further optimized as drug candidates. Owing to the mutability of precursor protein genes that encode their core structures and the availability of diverse posttranslational modification (PTM) enzymes with broad substrate tolerances, RiPP systems are well suited to engineer complex peptides with desired functions. [Display omitted] •Peptide diversification by posttranslational modification of precursor proteins.•Genome mining functionally diverse protein superfamilies yields RiPP novelty.•Natural antimicrobial modified peptides provide lead structures for optimization.•Promiscuous RiPP maturases are attractive tools for peptide engineering.•Engineering by targeted biosynthesis or screening gene-encoded peptide libraries.