A Plug-and-Play T7 Expression System for Heterologous Production of Lanthipeptides in Bacillus subtilis DOI
Chengyou Shi, Huimin Zhao

ACS Synthetic Biology, Journal Year: 2024, Volume and Issue: 13(11), P. 3746 - 3753

Published: Oct. 31, 2024

Ribosomally synthesized lanthionine-containing peptides (lanthipeptides) have emerged as a promising source of antimicrobials against multidrug resistance pathogens. An effective way to discover and engineer lanthipeptides is through heterologous expression their biosynthetic gene clusters (BGCs) in host choice. Here we report plug-and-play pathway refactoring strategy for rapid evaluation lanthipeptide BGCs Bacillus subtilis based on the T7 system. As proof concept, used this not only observe successful production known haloduracin β but also two new human-microbiota-derived that previously failed be produced Escherichia coli. The resulting B. system should enable genome mining high-throughput manner.

Language: Английский

Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases DOI Open Access
Mohamed Kamel,

Sami Aleya,

Majed Alsubih

et al.

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(2), P. 217 - 217

Published: Feb. 18, 2024

Infectious diseases have long posed a significant threat to global health and require constant innovation in treatment approaches. However, recent groundbreaking research has shed light on previously overlooked player the pathogenesis of disease-the human microbiome. This review article addresses intricate relationship between microbiome infectious unravels its role as crucial mediator host-pathogen interactions. We explore remarkable potential harnessing this dynamic ecosystem develop innovative strategies that could revolutionize management diseases. By exploring latest advances emerging trends, aims provide new perspective combating by targeting

Language: Английский

Citations

26

A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation DOI Creative Commons

Ziqi Ma,

Tao Zuo, Norbert Frey

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 23, 2024

Language: Английский

Citations

24

Advances in lasso peptide discovery, biosynthesis, and function DOI
Susanna E. Barrett, Douglas A. Mitchell

Trends in Genetics, Journal Year: 2024, Volume and Issue: 40(11), P. 950 - 968

Published: Aug. 31, 2024

Language: Английский

Citations

9

Antimicrobial Peptides Derived from Bacteria: Classification, Sources, and Mechanism of Action against Multidrug-Resistant Bacteria DOI Open Access

Raynichka Mihaylova-Garnizova,

Slavena Davidova,

Yordan Hodzhev

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10788 - 10788

Published: Oct. 8, 2024

Antimicrobial peptides (AMPs) are short, usually cationic with an amphiphilic structure, which allows them to easily bind and interact the cellular membranes of viruses, bacteria, fungi, other pathogens. Bacterial AMPs, or bacteriocins, can be produced from Gram-negative Gram-positive bacteria via ribosomal synthesis eliminate competing organisms. AMPs vital in addressing increasing antibiotic resistance various pathogens, potentially serving as alternative ineffective antibiotics. Bacteriocins have a narrow spectrum action, making highly specific antibacterial compounds that target particular bacterial This review covers two main groups bacteriocins by their modes classification, sources positive effects they play on human body, limitations future perspectives

Language: Английский

Citations

9

Iterative acylation on mature lasso peptides by widespread acetyltransferases for lipolasso production DOI Creative Commons

Jiang Xiong,

Sheng-Ze Wu,

Z. Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract The biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs) leverages iterative catalysis to enhance structural biological diversity. Traditionally, enzymes install multiple post-translational modifications (PTMs) on linear peptides, rather than mature RiPPs with intricate three-dimensional structures, which would require complex changes in substrate binding poses. Here, we present a prolific class GCN5-related N-acetyltransferases (GNATs) that iteratively consecutively acylate two Lys residues within the loop ring motifs lasso diverging from typical modification peptides—an unprecedented function for PTM enzymes. Utilizing high-resolution cryo-electron microscopy enzymatic reconstitution, mapped peptide pocket IatT pinpointed key involved demarcating distinct acetylation steps. Structure-based engineering IatT’s acetyl group recognition site expanded cavity accommodate longer-chain acyl groups, leading creation lipolasso novel ribosomal lipopeptide. This strategy can be applied any RiPP BGC encoding GNAT, facilitating efficient diversification rare lipopeptides. Graphic

Language: Английский

Citations

1

Cell-free synthetic biology for natural product biosynthesis and discovery DOI Creative Commons
Andrew J. Rice,

Tien T. Sword,

Kameshwari Chengan

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Cell free synthetic biology enables a broad range of approaches relevant to the generation, biosynthetic characterisation, bioengineering, activity profiling, and production complex natural products.

Language: Английский

Citations

1

Functional Antimicrobial Peptide-loaded 3D Scaffolds for Infected Bone Defect Treatment with AI and Multidimensional Printing DOI
Mengmeng Li, Pin-Yi Zhao, Jingwen Wang

et al.

Materials Horizons, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Infection is the most prevalent complication of fractures, particularly in open and often leads to severe consequences.

Language: Английский

Citations

8

Facile Method for Determining Lanthipeptide Stereochemistry DOI Creative Commons
Youran Luo, Shuyun Xu, Autumn M. Frerk

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(4), P. 1767 - 1773

Published: Jan. 17, 2024

Lanthipeptides make up a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). contain lanthionine methyllanthionine bis-amino acids have varying stereochemistry. The stereochemistry new lanthipeptides is often not determined because current methods require equipment standard in most laboratories. In this study, we developed facile, efficient, user-friendly method for detecting lanthipeptide stereochemistry, utilizing advanced Marfey's analysis with detection by liquid chromatography coupled mass spectrometry (LC-MS). Under optimized conditions, 0.05 mg peptide sufficient characterize five (methyl)lanthionines different using simple setup, which much lower limit than methods. addition, describe readily access standards three stereoisomers two been reported known lanthipeptides. workflow uses commonly used nonchiral column system offers scalable platform assist antimicrobial discovery. We illustrate its utility an example discovered genome mining.

Language: Английский

Citations

6

Advancements in the Application of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) DOI Creative Commons

Sang‐Woo Han,

Hyung‐Sik Won

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 479 - 479

Published: April 15, 2024

Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a significant potential for novel therapeutic applications because of their bioactive properties, stability, specificity. RiPPs are on ribosomes, followed by intricate post-translational modifications (PTMs), crucial diverse structures functions. PTMs, such as cyclization, methylation, proteolysis, play roles in enhancing RiPP stability bioactivity. Advances synthetic biology bioinformatics have significantly advanced the field, introducing new methods production engineering. These encompass strategies heterologous expression, genetic refactoring, exploiting substrate tolerance tailoring enzymes to create analogs with improved or entirely Furthermore, introduction implementation cutting-edge screening methods, including mRNA display, surface two-hybrid systems, expedited identification pharmaceutical potential. This comprehensive review not only discusses current advancements research but also promising opportunities that leveraging these presents, illustrating synergy between traditional biochemistry contemporary engineering approaches.

Language: Английский

Citations

4

Multi-omic analysis tools for microbial metabolites prediction DOI Creative Commons
Shengbo Wu, Haonan Zhou, Danlei Chen

et al.

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(4)

Published: May 23, 2024

Abstract How to resolve the metabolic dark matter of microorganisms has long been a challenging problem in discovering active molecules. Diverse omics tools have developed guide discovery and characterization various microbial metabolites, which make it gradually possible predict overall metabolites for individual strains. The combinations multi-omic analysis effectively compensates shortcomings current studies that focus only on single or broad class metabolites. In this review, we systematically update, categorize sort out different prediction last five years appeal combination understanding nature microbes. First, provide general survey updated databases, webservers, software based genomics, transcriptomics, proteomics, metabolomics, respectively. Then, discuss essentiality integration multi-omics data strains communities, as well stressing other techniques, such systems biology methods data-driven algorithms. Finally, identify key challenges trends developing more comprehensive diverse contribute human health disease treatment.

Language: Английский

Citations

4