Research progress on graspetide-like ribosomally synthesized and post-translationally modification peptide kind natural products

• 1、Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education),School of Pharmaceutical Sciences, Wuhan University, Wuhan 430072

Abstract：Microbial natural products are rich source of antibiotics. Modifying biosynthetic pathways of natural products to develop derivatives with excellent pharmacological activity has always been the important strategy to combat the antimicrobial resistance. Ribosomally synthesized and post-translationally modified peptides (RiPPs) consist of a large class of microbial natural products with potential antibiotic activity. The post-modification enzymes involved in the biosynthesis of RiPPs have broader substrate selection than non-ribosomal peptides and polyketide synthases, making RiPPs a group of natural products with greater engineering potential. More than 30 types of RiPPs have been discovered so far, which exhibit various biological activities such as antibacterial and antitumor. Graspetides are a kind of macrocyclization-modified RiPPs. This structural feature endows grapetides with good membrane permeability and stability, making them very advantageous in drug development. Graspetides can be divided into more than 24 groups according to the conserved sequence of their precursor peptides and the category of post-modification enzymes, implying that their biological assembly logic is complex and changeable. This review summarizes the biosynthetic mechanisms of representative graspetides newly discovered in recent years, aiming to provide ideas for the development of new graspetide-like natural products.

Keywords： Graspetide-like RiPPs Microbial natural products Biosynthesis Macrocyclization Biosynthesis progress