Abstract
Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides produced by microorganisms. The name lanthipeptide is derived from lanthionine, a thioether–bridged amino acid installed by dedicated modification enzymes. Serines and threonines are dehydrated and subsequently coupled to cysteines, thus forming intramolecular lanthionine rings. A well–known subclass of lanthipeptides are lantibiotics: lanthipeptides with antimicrobial activity. The lantibiotic nisin is applied worldwide in the food industry to prevent food spoilage. This review focuses on lanthipeptide leader peptides, which have a crucial and central role in lanthipeptide biosynthesis. Lanthipeptide leader peptides are present at the N–terminus within precursor lanthipeptides. Intriguingly, a single leader peptide can interact with highly different modifying enzyme(s) (domains) and furthermore induce export out of the cell via a dedicated export protein. Eventually the leader peptide is cleaved off by a leader peptidase, either extracellularly or intracellularly as part of the transporter. Recent exciting mechanistic and engineering studies ignited the unraveling of the fascinating interactions of lanthipeptide leader peptides with the lanthipeptide modification enzymes and transporters. The biosynthesis of at least some lanthipeptides is performed by a highly flexible enzyme system. Novel lantibiotics can be synthesized by fusing lanthipeptide leader peptides to completely different silent lantibiotics obtained by genome mining. Moreover, the fusion of leader peptides to the N–terminus of medically and economically important therapeutic peptides has resulted in lanthioninestabilized therapeutics with enhanced bioavailability and optimized receptor interaction.
Keywords: Lanthipeptide, lanthionine, lantibiotic, leader, nisin, dehydratase, cyclase
Current Protein & Peptide Science
Title:Mechanistic Aspects of Lanthipeptide Leaders
Volume: 14 Issue: 2
Author(s): Annechien Plat, Anneke Kuipers, Rick Rink and Gert N. Moll
Affiliation:
Keywords: Lanthipeptide, lanthionine, lantibiotic, leader, nisin, dehydratase, cyclase
Abstract: Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides produced by microorganisms. The name lanthipeptide is derived from lanthionine, a thioether–bridged amino acid installed by dedicated modification enzymes. Serines and threonines are dehydrated and subsequently coupled to cysteines, thus forming intramolecular lanthionine rings. A well–known subclass of lanthipeptides are lantibiotics: lanthipeptides with antimicrobial activity. The lantibiotic nisin is applied worldwide in the food industry to prevent food spoilage. This review focuses on lanthipeptide leader peptides, which have a crucial and central role in lanthipeptide biosynthesis. Lanthipeptide leader peptides are present at the N–terminus within precursor lanthipeptides. Intriguingly, a single leader peptide can interact with highly different modifying enzyme(s) (domains) and furthermore induce export out of the cell via a dedicated export protein. Eventually the leader peptide is cleaved off by a leader peptidase, either extracellularly or intracellularly as part of the transporter. Recent exciting mechanistic and engineering studies ignited the unraveling of the fascinating interactions of lanthipeptide leader peptides with the lanthipeptide modification enzymes and transporters. The biosynthesis of at least some lanthipeptides is performed by a highly flexible enzyme system. Novel lantibiotics can be synthesized by fusing lanthipeptide leader peptides to completely different silent lantibiotics obtained by genome mining. Moreover, the fusion of leader peptides to the N–terminus of medically and economically important therapeutic peptides has resulted in lanthioninestabilized therapeutics with enhanced bioavailability and optimized receptor interaction.
Export Options
About this article
Cite this article as:
Plat Annechien, Kuipers Anneke, Rink Rick and N. Moll Gert, Mechanistic Aspects of Lanthipeptide Leaders, Current Protein & Peptide Science 2013; 14 (2) . https://dx.doi.org/10.2174/1389203711314020001
DOI https://dx.doi.org/10.2174/1389203711314020001 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Role of ROS and RNS in Regulating Life and Death of Blood Monocytes
Current Pharmaceutical Design Coronavirus (COVID-19) and Employee Health
Coronaviruses Heterogeneous Catalysis in the Meerwein-Ponndorf-Verley Reduction of Carbonyl Compounds
Current Organic Chemistry Other Activities
Current Bioactive Compounds Free ISG15 and Protein ISGylation Emerging in SARS-CoV-2 Infection
Current Drug Targets Recent Advances in Controlled Release Pulmonary Therapy
Current Drug Delivery Heterocyclic N-Oxides - An Emerging Class of Therapeutic Agents
Current Medicinal Chemistry RNA Coronaviruses’ Outbreaks: Recent Progress on the SARS-CoV-2 Pandemic Diagnostic Tests, Vaccination and Therapeutics
Mini-Reviews in Medicinal Chemistry Dissecting the Therapeutic Potency of Antimicrobial Peptides Against Microbial Biofilms
Current Protein & Peptide Science Preparation and In vitro Evaluation of Efficacy and Toxicity of Polysorbate 80-coated Bovine Serum Albumin Nanoparticles containing Amphotericin B
Current Drug Delivery Bacteriophages and Phage-Derived Proteins – Application Approaches
Current Medicinal Chemistry Lipid Rafts and Redox Regulation of Cellular Signaling in Cholesterol Induced Atherosclerosis
Current Cardiology Reviews Pd/C-mediated Synthesis of 3-methyleneisoindolin-1-ones: Biological and Theoretical Study of their PDE4 Inhibition
Letters in Drug Design & Discovery The PKB/AKT Pathway in Cancer
Current Pharmaceutical Design Pharmacological and Clinical Basis of Treatment of Familial Mediterranean Fever (FMF) with Colchicine or Analogues: An Update
Current Drug Targets - Inflammation & Allergy Design, Synthesis and Evaluation of Hybrid 2-Heteroaryl Benzimidazole- Chalcone Derivatives as Anticancer Agents
Letters in Organic Chemistry Isolation of Natural Compounds from Syzygium densiflorum Fruits and Exploring its Chemical Property, Therapeutic Role in Diabetic Management
The Natural Products Journal Recent Patents of Complementary and Alternative Medicine for Allergic Rhinitis
Recent Patents on Inflammation & Allergy Drug Discovery Applications of Dimedone in the Synthesis of Heterocycles: An Update
Current Organic Chemistry Development of Anti-HIV Agents Targeting Dynamic Supramolecular Mechanism: Entry and Fusion Inhibitors Based on CXCR4/CCR5 Antagonists and gp41-C34-Remodeling Peptides
Current HIV Research