{"title":"Bacterial Cytochrome P450 Catalyzed Macrocyclization of Ribosomal Peptides","authors":"Jing Liu, Runze Liu, Bei-Bei He, Xiaoqian Lin, Longcheng Guo, Gengfan Wu and Yong-Xin Li*, ","doi":"10.1021/acsbiomedchemau.4c0008010.1021/acsbiomedchemau.4c00080","DOIUrl":null,"url":null,"abstract":"<p >Macrocyclization is a vital process in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), significantly enhancing their structural diversity and biological activity. Universally found in living organisms, cytochrome P450 enzymes (P450s) are versatile catalysts that facilitate a wide array of chemical transformations and have recently been discovered to contribute to the expansion and complexity of the chemical spectrum of RiPPs. Particularly, P450-catalyzed biaryl-bridged RiPPs, characterized by highly modified structures, represent an intriguing but underexplored class of natural products, as demonstrated by the recent discovery of tryptorubin A, biarylitide and cittilin. These P450 enzymes demonstrate their versatility by facilitating peptide macrocyclization through the formation of carbon–carbon (C–C), carbon–nitrogen (C–N) and ether bonds between the side chains of tyrosine (Tyr), tryptophan (Trp) and histidine (His). This Review briefly highlights the latest progress in P450-catalyzed macrocyclization within RiPP biosynthesis, resulting in the generation of structurally complex RiPPs. These findings have expedited the discovery and detailed analysis of new P450s engaged in RiPP biosynthetic pathways.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"4 6","pages":"268–279 268–279"},"PeriodicalIF":3.8000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomedchemau.4c00080","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Bio & Med Chem Au","FirstCategoryId":"1085","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsbiomedchemau.4c00080","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Macrocyclization is a vital process in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), significantly enhancing their structural diversity and biological activity. Universally found in living organisms, cytochrome P450 enzymes (P450s) are versatile catalysts that facilitate a wide array of chemical transformations and have recently been discovered to contribute to the expansion and complexity of the chemical spectrum of RiPPs. Particularly, P450-catalyzed biaryl-bridged RiPPs, characterized by highly modified structures, represent an intriguing but underexplored class of natural products, as demonstrated by the recent discovery of tryptorubin A, biarylitide and cittilin. These P450 enzymes demonstrate their versatility by facilitating peptide macrocyclization through the formation of carbon–carbon (C–C), carbon–nitrogen (C–N) and ether bonds between the side chains of tyrosine (Tyr), tryptophan (Trp) and histidine (His). This Review briefly highlights the latest progress in P450-catalyzed macrocyclization within RiPP biosynthesis, resulting in the generation of structurally complex RiPPs. These findings have expedited the discovery and detailed analysis of new P450s engaged in RiPP biosynthetic pathways.
期刊介绍:
ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.