Yanli Xu, Fleur Ruijne, Manel Garcia Diez, Jorrit Jilles Stada, Oscar P. Kuipers
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引用次数: 0
Abstract
The growing threat of antibiotic resistance highlights the urgent need for new antimicrobial agents. Nonribosomal peptides (NRPs) are potent antibiotics with complex structures, but generating novel NRP analogues is costly and inefficient. An emerging alternative is using ribosomally synthesized and post-translationally modified peptides (RiPPs), which are gene-encoded, allowing for easier mutagenesis and modification. This study aimed to produce peptides with two key structural elements of many NRP antibiotics: a macrocycle and an N-terminal lipid moiety. The RiPP enzymes SyncM and PirF were employed-SyncM introduced lanthionine or methyllanthionine macrocycles, while PirF incorporated isoprenyl chains to emulate the lipid moieties in NRPs. Both enzymes successfully modified the templates, and their combined use generated lipidated macrocyclic peptides, resembling lipopeptide antibiotics. These findings demonstrate the potential of SyncM and PirF as versatile tools for designing novel gene-encoded NRP mimics, enabling high-throughput screening for new bioactive peptides.
期刊介绍：
Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine.
Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.
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