Investigating the Specificity of the Dehydration and Cyclization Reactions in Engineered Lanthipeptides by Synechococcal SyncM DOI Creative Commons
Patricia Arias-Orozco, Yunhai Yi, Fleur Ruijne

et al.

ACS Synthetic Biology, Journal Year: 2022, Volume and Issue: 12(1), P. 164 - 177

Published: Dec. 15, 2022

ProcM-like enzymes are class II promiscuous lanthipeptide synthetases that an attractive tool in synthetic biology for producing lanthipeptides with biotechnological or clinically desired properties. SyncM is a recently described modification enzyme from this family used to develop versatile expression platform engineering lanthipeptides. Most remarkably, can modify up 79 SyncA substrates single strain. Six SyncAs were previously characterized pool of substrates. They showed particular characteristics, such as the presence one two lanthionine rings, different flanking residues influencing ring formation, and directions, demonstrating relaxed specificity toward its precursor peptides. To gain deeper understanding potential biosynthetic tool, we further explored enzyme′s capabilities limits dehydration formation. We scaffolds peptide engineering, including changes ring′s directionality (relative position Ser/Thr Cys peptide) size. aimed rationally design mimetics cyclic antimicrobials introduce macrocycles prochlorosin-related nonrelated This study highlights largest 15 amino acids (ring-forming included) date. Taking advantage acid substrate tolerance SyncM, designed first single-SyncA-based antimicrobial. The insights gained work will aid future bioengineering studies. Additionally, it broadens SyncM′s application scope introducing other bioactive molecules.

Language: Английский

After a century of nisin research - where are we now? DOI Creative Commons
Des Field, Miguel Fernández de Ullivarri, R. Paul Ross

et al.

FEMS Microbiology Reviews, Journal Year: 2023, Volume and Issue: 47(3)

Published: May 1, 2023

It is almost a century since nisin was discovered in fermented milk cultures, coincidentally the same year that penicillin first described. Over last 100 years this small, highly modified pentacyclic peptide has not only found success food industry as preservative but also served paradigm for our understanding of genetic organization, expression and regulation genes involved lantibiotic biosynthesis - one few cases extensive post-translation modification prokaryotes. Recent developments complex have shed light on cellular location transport machinery co-ordinated series spatio-temporal events required to produce active provide resistance immunity. The continued unearthing new natural variants from within human animal gastrointestinal tracts sparked interest potential application influence microbiome, given growing recognition role microbiota plays health disease. Moreover, interdisciplinary approaches taken advantage biotechnological advancements bioengineer novel expand functionality applications biomedical field. This review will discuss latest progress these aspects research.

Language: Английский

Citations

56

Cell-free biosynthesis and engineering of ribosomally synthesized lanthipeptides DOI Creative Commons
Wanqiu Liu,

Xiangyang Ji,

Fang Ba

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 21, 2024

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with diverse chemical structures potent biological activities. A vast majority RiPP gene clusters remain unexplored in microbial genomes, which is partially due to the lack rapid efficient heterologous expression systems for characterization biosynthesis. Here, we report unified biocatalysis (UniBioCat) system based on cell-free biosynthesis engineering RiPPs. We demonstrate UniBioCat by reconstituting full biosynthetic pathway de novo salivaricin B, lanthipeptide RiPP. Next, delete several protease/peptidase genes from source strain enhance performance UniBioCat, then can synthesize screen B variants enhanced antimicrobial activity. Finally, show that generalizable synthesizing evaluating bioactivity ten uncharacterized lanthipeptides. expect accelerate discovery, characterization, synthesis

Language: Английский

Citations

22

Microbial secondary metabolites: advancements to accelerate discovery towards application DOI
Jaime Lorenzo N. Dinglasan, Hiroshi Otani, Drew T. Doering

et al.

Nature Reviews Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

Citations

3

Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra DOI
Andrew King, Zhengan Zhang,

Emerson Glassey

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(12), P. 2420 - 2434

Published: Nov. 16, 2023

Language: Английский

Citations

35

Bacillus licheniformis: A Producer of Antimicrobial Substances, including Antimycobacterials, Which Are Feasible for Medical Applications DOI Creative Commons
Margarita O. Shleeva, Daria A. Kondratieva,

Arseny S. Kaprelyants

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(7), P. 1893 - 1893

Published: July 5, 2023

Bacillus licheniformis produces several classes of antimicrobial substances, including bacteriocins, which are peptides or proteins with different structural composition and molecular mass: ribosomally synthesized by bacteria (1.4-20 kDa), non-ribosomally cyclic lipopeptides (0.8-42 kDa) exopolysaccharides (>1000 kDa). Different bacteriocins act against Gram-positive Gram-negative bacteria, fungal pathogens amoeba cells. The main mechanisms bacteriocin lytic activity include interaction membranes target cells resulting in alterations, pore-forming, inhibition cell wall biosynthesis. DNase RNase for some bacteriocines also postulated. Non-ribosomal special non-ribosomal multimodular peptide synthetases contain unnatural amino acids fatty acids. Their harmful effect is due to their ability form pores biological membranes, destabilize lipid packaging, disrupt the peptidoglycan layer. Lipopeptides, as biosurfactants, able destroy bacterial biofilms. Secreted polysaccharides high weight compounds, composed repeated units sugar moieties attached a carrier lipid. antagonistic action was revealed relation viruses, fungi. Exopolysaccharides inhibit formation biofilms pathogenic prevent colonization on various surfaces. However, mechanism many secreted antibacterial substances remains unknown. most has been studied vitro only, but have characterized vivo they found practical applications medicine veterinary. that surfactant properties used industries. In this review, attention paid antimycobacterials produced B. possible approach combat multidrug-resistant latent tuberculosis. particular, licheniformins bacitracins shown strong antimycobacterial activity. medical application antibacterials promising limited toxicity animals humans. As such, similar enhancement natural achieved using genetic engineering, reduction same appears feasible. unique capability synthesize produce range compounds means organism can universal vehicle antibiotic probiotic cultures strains types pathogens, mycobacteria.

Language: Английский

Citations

23

Navigating Antibacterial Frontiers: A Panoramic Exploration of Antibacterial Landscapes, Resistance Mechanisms, and Emerging Therapeutic Strategies DOI Creative Commons

Krittika Ralhan,

Kavita A. Iyer, Leilani Lotti Díaz

et al.

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(5), P. 1483 - 1519

Published: May 1, 2024

The development of effective antibacterial solutions has become paramount in maintaining global health this era increasing bacterial threats and rampant antibiotic resistance. Traditional antibiotics have played a significant role combating infections throughout history. However, the emergence novel resistant strains necessitates constant innovation research. We analyzed data on antibacterials from CAS Content Collection, largest human-curated collection published scientific knowledge, which proven valuable for quantitative analysis knowledge. Our focuses mining Collection recent publications (since 2012). This article aims to explore intricate landscape research while reviewing advancement traditional emerging strategies. By delving into resistance mechanisms, paper highlights need find alternate strategies address growing concern.

Language: Английский

Citations

15

Emerging strategies and therapeutic innovations for combating drug resistance in Staphylococcus aureus strains: A comprehensive review DOI
Mohanraj Gopikrishnan, Sree Haryini,

C. George Priya Doss

et al.

Journal of Basic Microbiology, Journal Year: 2024, Volume and Issue: 64(5)

Published: Feb. 2, 2024

Abstract In recent years, antibiotic therapy has encountered significant challenges due to the rapid emergence of multidrug resistance among bacteria responsible for life‐threatening illnesses, creating uncertainty about future management infectious diseases. The escalation antimicrobial in post‐COVID era compared pre‐COVID raised global concern. prevalence nosocomial‐related infections, especially outbreaks drug‐resistant strains Staphylococcus aureus , have been reported worldwide, with India being a notable hotspot such occurrences. Various virulence factors and mutations characterize nosocomial infections involving S. . lack proper alternative treatments leading increased drug emphasizes need investigate examine research combat pandemics. current genomics era, application advanced technologies as next‐generation sequencing (NGS), machine learning (ML), quantum computing (QC) genomic analysis prediction significantly pace diagnosing pathogens insights into genetic intricacies. Despite prompt diagnosis, elimination remains unattainable absence effective therapies. Researchers are exploring various therapeutic approaches, including phage therapy, peptides, photodynamic vaccines, host‐directed therapies, more. proposed review mainly focuses on journey over past decade, detailing its mechanisms, subcontinent, innovations diagnosis strains, applicants NGS ML along QC, it helps design novel therapeutics approaches against infection.

Language: Английский

Citations

14

A review of the role of probiotics for the control of viral diseases in aquaculture DOI
Sourav Chattaraj, Arindam Ganguly, Asish Mandal

et al.

Aquaculture International, Journal Year: 2022, Volume and Issue: 30(5), P. 2513 - 2539

Published: June 18, 2022

Language: Английский

Citations

30

Beneficial modulation of human health in the oral cavity and beyond using bacteriocin-like inhibitory substance-producing streptococcal probiotics DOI Creative Commons
John Tagg, Liam K. Harold, Rohit Jain

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: March 28, 2023

The human oral cavity contains a diversity of microbial habitats that have been adopted and adapted to as homeland by an amazingly heterogeneous population microorganisms collectively referred the microbiota. These microbes generally co-habit in harmonious homeostasis. However, under conditions imposed stress, with changes host’s physiology or nutritional status, response foreign antimicrobial incursions, some components “microbiome” (viz. situ microbiota) may enter dysbiotic state. This microbiome dysbiosis can manifest variety guises including streptococcal sore throats, dental caries, thrush, halitosis periodontal disease. Most strategies currently available for management treatment diseases focus on repetitive “broad sweep” short-term culling microbe populations, hopefully perceived principal pathogens. Both physical chemical techniques are used. application more focused approaches harnessing elimination key pathogens is now feasible through use probiotic strains naturally colonization also equipped produce anti-competitor molecules such bacteriocins bacteriocin-like inhibitory substances (viz BLIS). Some these probiotics capable suppressing proliferation recognized mouth, thereby assisting restoration BLIS K12 M18, progenitors BLIS-producing probiotics, members commensal species Streptococcus salivarius. More recently however, number other non-streptococcal candidate promoted. What becoming increasingly apparent future applications will probably extend well beyond attempted limitation direct pathological consequences encompass plethora systemic disorders host. background evolving prospects beneficial modulation via S. salivarius comprises present review.

Language: Английский

Citations

19

Staphylococcus epidermidis bacteriocin A37 kills natural competitors with a unique mechanism of action DOI Creative Commons
Jan-Samuel Puls, Benjamin Winnerling, Jeffrey J. Power

et al.

The ISME Journal, Journal Year: 2024, Volume and Issue: 18(1)

Published: Jan. 1, 2024

Abstract Many bacteria produce antimicrobial compounds such as lantibiotics to gain advantage in the competitive natural environments of microbiomes. Epilancins constitute an until now underexplored family with unknown ecological role and unresolved mode action. We discovered production epilancin nasal isolate Staphylococcus epidermidis A37. Using bioinformatic tools, we found that epilancins are frequently encoded within staphylococcal genomes, highlighting their relevance. demonstrate A37 contributes competition specifically against corynebacterial competitors. Combining microbiological approaches quantitative vivo vitro fluorescence microscopy cryo-electron tomography, show enters cytoplasm through a partially transmembrane-potential-driven uptake without impairing cell membrane function. Upon intracellular aggregation, induces formation vesicles, which heavily loaded compound essential for antibacterial activity epilancin. Our work sheds light on staphylococci mediated by action previously lantibiotics.

Language: Английский

Citations

7