Unveiling novel antimicrobial peptides from the ruminant gastrointestinal microbiomes: A deep learning-driven approach yields an anti-MRSA candidate

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Antimicrobial peptides (AMPs) present a promising avenue to combat the growing threat of antibiotic resistance. The ruminant gastrointestinal microbiome serves as unique ecosystem that offers untapped potential for AMP discovery.

Language: Английский

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Genome mining and heterologous expression reveal streptacidin, a new lasso peptide from Streptacidiphilus jiangxiensis

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We heterologously produced a type II lasso peptide gene cluster that was mined from Streptacidiphilus jiangxiensis in E. coli . Streptacidin is the first documented to maintain its 3D structure with methionine as steric lock.

Language: Английский

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Metabolic engineering approaches for the biosynthesis of antibiotics

Microbial Cell Factories, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 31, 2025

Antibiotics have been saving countless lives from deadly infectious diseases, which we now often take for granted. However, are currently witnessing a significant rise in the emergence of multidrug-resistant (MDR) bacteria, making these infections increasingly difficult to treat hospitals. The discovery and development new antibiotic has slowed, largely due reduced profitability, as antibiotics lose effectiveness quickly pathogenic bacteria evolve into MDR strains. To address this challenge, metabolic engineering recently become crucial developing efficient enzymes cell factories capable producing both existing wide range derivatives analogs. In paper, review recent tools strategies synthetic biology production antibiotics, their derivatives, analogs, along with representative examples. These offer promising potential revitalize providing renewed hope humanity's fight against bacteria.

Language: Английский

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Role of Microbiome in Defense

Published: Jan. 1, 2025

Language: Английский

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Heterologous Expression of a Cryptic BGC from Bilophila sp. Provides Access to a Novel Family of Antibacterial Thiazoles

ACS Synthetic Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Human health is greatly influenced by the gut microbiota and imbalance can lead to development of diseases. It widely acknowledged that interaction bacteria within competitive ecosystems their specialized metabolites, which act, e.g., as antibacterials or siderophores. However, our understanding occurrence impact such natural products in human microbiome remains very limited. As arylthiazole siderophores are an emerging family growth-promoting molecules pathogenic bacteria, we analyzed a metagenomic data set from thereby identified bil-BGC, originates uncultured Bilophila strain. Through gene synthesis BGC assembly, heterologous expression mutasynthetic experiments, discovered bilothiazoles A–F. While established activities related indicate involvement metal-binding -uptake, could promote growth strains, also found antibiotic activity for some bilothiazoles. This supported biosensor-experiments, where C E show PrecA-suppressing activity, while bilothiazole F induces PblaZ, biosensor characteristic β-lactam antibiotics. These findings serve starting point investigating role pathogenicity species gut.

Language: Английский

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Bifidobacterium bacteriocins efficiently inhibit Clostridium perfringens and facilitate repair of infection damage: Application informed by intestinal niche

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106298 - 106298

Published: March 1, 2025

Language: Английский

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Synthetic Biology in Natural Product Biosynthesis

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

Published: March 21, 2025

Synthetic biology has played an important role in the renaissance of natural products research during post-genomics era. The development and integration new tools have transformed workflow product discovery engineering, generating multidisciplinary interest field. In this review, we summarize recent developments biosynthesis from three different aspects. First, advances bioinformatics, experimental, analytical to identify associated with predicted biosynthetic gene clusters (BGCs) will be covered. This followed by extensive review on heterologous expression bacterial, fungal plant organisms. native host-independent paradigm identification, pathway characterization, enzyme is where synthetic most prominent role. Lastly, strategies engineer pathways for structural diversification complexity generation discussed, including assembly-line megasynthase precursor-directed modification, combinatorial biosynthesis.

Language: Английский

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Large-scale biosynthetic analysis of human microbiomes reveals diverse protective ribosomal peptides

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 28, 2025

The human microbiome produces diverse metabolites that influence host health, yet the chemical landscape of ribosomally synthesized and post-translationally modified peptides (RiPPs)-a versatile class bioactive compounds-remains underexplored. Here, we conduct a large-scale biosynthetic analysis 306,481 microbial genomes from human-associated microbiomes, uncovering broad array yet-to-be-discovered RiPPs. These RiPPs are distributed across various body sites but show specific enrichment in gut oral microbiome. Big data omics reveals numerous RiPP families inversely related to diseases, suggesting their potential protective effects on health. For proof principle study, apply synthetic-bioinformatic natural product (syn-BNP) approach chemically synthesize nine autoinducing (AIPs) for vitro ex vivo assay. Our findings reveal five AIPs effectively inhibit biofilm formation disease-associated pathogens. Furthermore, when testing microbiota mice with inflammatory bowel disease, observe two can regulate community reduce harmful species. highlight vast regulating communities maintaining emphasizing therapeutic development.

Language: Английский

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

Published: Aug. 11, 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

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Bacillus halotolerans attenuates inflammation induced by enterotoxigenic Escherichia coli infection in vivo and in vitro based on its metabolite soyasaponin I regulating the p105-Tpl2-ERK pathway

Food & Function, Journal Year: 2024, Volume and Issue: 15(12), P. 6743 - 6758

Published: Jan. 1, 2024

Soyasaponins, recognized for their anti-inflammatory and antioxidant effects, have not yet been fully explored role in combating enterotoxigenic Escherichia coli (ETEC) infections.

Language: Английский

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