{"title":"通过引入大量的RiPP修饰来获得新的天然生物活性肽。","authors":"Yuxin Fu, Yanli Xu, Fleur Ruijne, Oscar P Kuipers","doi":"10.1093/femsre/fuad017","DOIUrl":null,"url":null,"abstract":"<p><p>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 post-translationally 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.</p>","PeriodicalId":12201,"journal":{"name":"FEMS microbiology reviews","volume":"47 3","pages":""},"PeriodicalIF":10.1000,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373908/pdf/","citationCount":"1","resultStr":"{\"title\":\"Engineering lanthipeptides by introducing a large variety of RiPP modifications to obtain new-to-nature bioactive peptides.\",\"authors\":\"Yuxin Fu, Yanli Xu, Fleur Ruijne, Oscar P Kuipers\",\"doi\":\"10.1093/femsre/fuad017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 post-translationally 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.</p>\",\"PeriodicalId\":12201,\"journal\":{\"name\":\"FEMS microbiology reviews\",\"volume\":\"47 3\",\"pages\":\"\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2023-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373908/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"FEMS microbiology reviews\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/femsre/fuad017\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEMS microbiology reviews","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/femsre/fuad017","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 1
摘要
天然生物活性肽的发现是一个具有挑战性和耗时的过程。然而,合成生物学的进步为肽工程提供了有希望的新途径,允许使用已知肽作为模板设计和生产各种具有增强或新的生物活性的新天然肽。蓝硫肽是核糖体合成和翻译后修饰的肽(RiPPs)。蓝硫肽固有的翻译后修饰(PTM)酶和核糖体生物合成的模块化使其能够以高通量的方式进行工程和筛选。随着许多新的ptm及其相关修饰酶被鉴定和表征,RiPPs研究领域正在迅速发展。这些多样和混杂的修饰酶所呈现的模块化使它们成为进一步在体内工程的有希望的工具,允许其结构和活性的多样化。本文综述了RiPPs中发生的各种修饰,并讨论了各种修饰酶在硫肽工程中的潜在应用和可行性。我们强调了lanthipeptide- and RiPP-engineering的前景,以生产和筛选新的肽,包括强效的非核糖体产生的抗菌肽(nrp)的模拟物,如达托霉素、万古霉素和teixobactin,它们具有很高的治疗潜力。
Engineering lanthipeptides by introducing a large variety of RiPP modifications to obtain new-to-nature bioactive peptides.
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 post-translationally 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.
期刊介绍:
Title: FEMS Microbiology Reviews
Journal Focus:
Publishes reviews covering all aspects of microbiology not recently surveyed
Reviews topics of current interest
Provides comprehensive, critical, and authoritative coverage
Offers new perspectives and critical, detailed discussions of significant trends
May contain speculative and selective elements
Aimed at both specialists and general readers
Reviews should be framed within the context of general microbiology and biology
Submission Criteria:
Manuscripts should not be unevaluated compilations of literature
Lectures delivered at symposia must review the related field to be acceptable