Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits DOI Creative Commons

Seung-Gyun Woo,

Seong Keun Kim, Seung‐Goo Lee

et al.

Journal of Biological Engineering, Journal Year: 2025, Volume and Issue: 19(1)

Published: Jan. 21, 2025

Abstract Background As our understanding of gut microbiota’s metabolic impacts on health grows, the interest in engineered probiotics has intensified. This study aimed to engineer probiotic Escherichia coli Nissle 1917 (EcN) produce indoleacetic acid (IAA) response inflammatory biomarkers thiosulfate and nitrate. Results Genetic circuits were developed initiate IAA synthesis upon detecting signals, optimizing a heterologous biosynthetic pathway, incorporating RiboJ insulator enhance production. The EcN strains demonstrated increased production presence An IAA-responsive genetic circuit using IacR transcription factor from Pseudomonas putida 1290 was also for real-time monitoring. Conclusions Given IAA’s role reducing gastrointestinal inflammation, further refinement this strain could lead effective, situ IAA-based therapies. proof-of-concept advances field live biotherapeutic products offers promising approach targeted therapy bowel diseases.

Language: Английский

Importance of Bacteroidetes in host–microbe interactions and ecosystem functioning DOI

Xinya Pan,

Jos M. Raaijmakers, Víctor J. Carrión

et al.

Trends in Microbiology, Journal Year: 2023, Volume and Issue: 31(9), P. 959 - 971

Published: May 10, 2023

Language: Английский

Citations

92

Microbiome composition modulates secondary metabolism in a multispecies bacterial community DOI Creative Commons
Marc G. Chevrette, Chris S. Thomas, Amanda Hurley

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(42)

Published: Oct. 10, 2022

Bacterial secondary metabolites are a major source of antibiotics and other bioactive compounds. In microbial communities, these molecules can mediate interspecies interactions responses to environmental change. Despite the importance in human health ecology, little is known about their roles regulation context multispecies communities. simplified model rhizosphere composed Bacillus cereus , Flavobacterium johnsoniae Pseudomonas koreensis we show that dynamics metabolism depend on community species composition interactions. Comparative metatranscriptomics metametabolomics reveal abundance transcripts biosynthetic gene clusters (BGCs) metabolomic molecular features differ between monocultures or dual cultures tripartite community. both two- three-member cocultures, P. modified expression BGCs for zwittermicin, petrobactin, B. F. johnsoniae, whereas BGC transcriptional response itself was minimal. Pairwise cocultures with displayed unique appear be derivatives lokisin, suggesting metabolic handoffs species. Deleting koreenceine, another metabolite, altered transcript metabolite profiles across community, including substantial up-regulation petrobactin bacillibactin koreenceine represses siderophore production. Results from this bacterial chemical output identity capacity coculture partners, microbiome may shape nature.

Language: Английский

Citations

71

Enhancing chemical and biological diversity by co-cultivation DOI Creative Commons
Denise Medeiros Selegato, Ian Castro‐Gamboa

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

Published: Feb. 1, 2023

In natural product research, microbial metabolites have tremendous potential to provide new therapeutic agents since extremely diverse chemical structures can be found in the nearly infinite population. Conventionally, these specialized are screened by single-strain cultures. However, owing lack of biotic and abiotic interactions monocultures, growth conditions significantly different from those encountered a environment result less diversity frequent re-isolation known compounds. last decade, several methods been developed eventually understand physiological under which cryptic genes activated an attempt stimulate their biosynthesis elicit production hitherto unexpressed diversity. Among those, co-cultivation is one most efficient ways induce silenced pathways, mimicking competitive for holistic regulation metabolites, has become golden methodology metabolome expansion. It does not require previous knowledge signaling mechanism genome nor any special equipment cultivation data interpretation. Several reviews shown produce biologically active leads. only few studies detailed experimental, analytical, microbiological strategies efficiently inducing bioactive molecules co-culture. Therefore, we reviewed applying co-culture secondary metabolite pathways insights into experimental variables compatible with high-throughput analytical procedures. Mixed-fermentation publications 1978 2022 were assessed regarding types set-ups, metabolic induction, interaction effects.

Language: Английский

Citations

37

The Use of Synthetic Microbial Communities to Improve Plant Health DOI
Samuel J. Martins,

Josephine Pasche,

Hiago Antonio Oliveira da Silva

et al.

Phytopathology, Journal Year: 2023, Volume and Issue: 113(8), P. 1369 - 1379

Published: March 1, 2023

Despite the numerous benefits plants receive from probiotics, maintaining consistent results across applications is still a challenge. Cultivation-independent methods associated with reduced sequencing costs have considerably improved overall understanding of microbial ecology in plant environment. As result, now, it possible to engineer consortium microbes aiming for health. Such synthetic communities (SynComs) contain carefully chosen species produce desired microbiome function. Microbial biofilm formation, production secondary metabolites, and ability induce resistance are some traits consider when designing SynComs. Plant-associated not assembled randomly. Ecological theories suggest that these defined phylogenetic organization structured by general community assembly rules. Using machine learning, we can study rules target functions generate phenotypes. Well-structured assemblages more likely lead stable SynCom thrives under environmental stressors as compared classical selection single activities or taxonomy. However, ensuring colonization long-term phenotype stability one challenges overcome SynComs, may change over time horizontal gene transfer retained mutations. Here, explored advances made research regarding health, focusing on bacteria, they most dominant form other members commonly found studies.

Language: Английский

Citations

37

Frenemies of the soil: Bacillus and Pseudomonas interspecies interactions DOI Creative Commons
Mark Lyng, Ákos T. Kovács

Trends in Microbiology, Journal Year: 2023, Volume and Issue: 31(8), P. 845 - 857

Published: March 4, 2023

Bacillus and Pseudomonas ubiquitously occur in natural environments are two of the most intensively studied bacterial genera soil. They often coisolated from environmental samples, as a result, several studies have experimentally cocultured bacilli pseudomonads to obtain emergent properties. Even so, general interaction between members these is virtually unknown. In past decade, data on interspecies interactions isolates has become more detailed, now, molecular permit mapping mechanisms behind their pairwise ecology. This review addresses current knowledge about microbe–microbe strains discusses how we can attempt generalize taxonomic level.

Language: Английский

Citations

35

Diversity and distribution of biosynthetic gene clusters in agricultural soil microbiomes DOI Creative Commons
Zhiguo Zhang, Lu Zhang, Lihan Zhang

et al.

mSystems, Journal Year: 2024, Volume and Issue: 9(4)

Published: March 12, 2024

ABSTRACT Bacterial secondary metabolites serve as an important source of molecules for drug discovery. They also play function in mediating the interactions microbial producers with their living environment and surrounding organisms. However, little is known about genetic novelty, distribution, community-level impacts soil bacterial biosynthetic potential on a large geographic scale. Here, we constructed first catalog 11,149 gene clusters (BGCs) from agricultural soils across China unearthed hidden new natural product discovery not-yet-cultivated bacteria. Notably, revealed pH strongest environmental driver BGC biogeography predicted that acidification global climate change could damage microbiome. The co-occurrence network genomes two BGC-rich species, i.e., Nocardia niigatensis Actinobacteriota PSRF01 Acidobacteriota, module hub connector, respectively, indicating keystone positions communities. We uncovered dominant role BGC-inferred biotic over drivers structuring Overall, this study achieved novel insights into landscape China, substantially expanding our understanding diversity novelty metabolism microbiota assembly. IMPORTANCE not only foundation numerous therapeutics (e.g., antibiotics anticancer drugs), but they critical ecological roles competition communication). knowledge limited to small fraction cultured strains, thus restricting comprehensive diversity, ecosystems. used culture-independent metagenomics explore potentials China. Our analyses high degree within environments, offering valuable biochemists seeking synthesize bioactive products. Furthermore, pivotal species communities significant relationship between richness phylogenetic turnover. This information emphasizes importance assembly

Language: Английский

Citations

10

Targeted genome mining with GATOR-GC maps the evolutionary landscape of biosynthetic diversity DOI Creative Commons
José D. D. Cediel-Becerra, Andrés Cumsille, Sebastian Guerra

et al.

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

Published: Feb. 28, 2025

Gene clusters, groups of physically adjacent genes that work collectively, are pivotal to bacterial fitness and valuable in biotechnology medicine. While various genome mining tools can identify characterize gene they often overlook their evolutionary diversity, a crucial factor revealing novel cluster functions applications. To address this gap, we developed GATOR-GC, targeted tool enables comprehensive flexible exploration clusters single execution. We show GATOR-GC identified diversity over 4 million similar experimentally validated biosynthetic (BGCs) other fail detect. highlight the utility previously uncharacterized co-occurring conserved potentially involved mycosporine-like amino acid biosynthesis mapped taxonomic patterns genomic islands modify DNA with 7-deazapurines. Additionally, its proximity-weighted similarity scoring, successfully differentiated BGCs FK-family metabolites (e.g., rapamycin, FK506/520) according chemistries. anticipate will be assess for targeted, exploratory, mining. is available at https://github.com/chevrettelab/gator-gc .

Language: Английский

Citations

1

Disentangling microbial interaction networks DOI Creative Commons
Leonardo Oña,

Shryli K Shreekar,

Christian Kost

et al.

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The structure and function of microbial communities is shaped by intricate ecological interactions amongst the constituent microorganisms. Thus, a mechanistic understanding emergent community-level functions requires knowledge on how architecture underlying interaction networks affects these properties. To address this, researchers employ different sequencing-based experimental approaches to infer topology given network. However, it remains generally unclear which method best suited for quantifying critical network parameters. Here we provide comparative overview serving this purpose, with particular emphasis their strengths weaknesses. In way, our work can help guide design studies that aim at unraveling structure-function relationships in communities.

Language: Английский

Citations

1

Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle DOI Open Access
Alexander A. Zhgun

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 11184 - 11184

Published: July 6, 2023

Filamentous fungi are one of the most important producers secondary metabolites. Some them can have a toxic effect on human body, leading to diseases. On other hand, they widely used as pharmaceutically significant drugs, such antibiotics, statins, and immunosuppressants. A single fungus species in response various signals produce 100 or more Such signaling is possible due coordinated regulation several dozen biosynthetic gene clusters (BGCs), which mosaically localized different regions fungal chromosomes. Their includes levels, from pathway-specific regulators, whose genes inside BGCs, global regulators cell (taking into account changes pH, carbon consumption, etc.) metabolism (affecting epigenetic driven by velvet family proteins, LaeA, etc.). In addition, low-molecular-weight substances mediating regulatory processes. This review devoted critical analysis available data "turning on" "off" biosynthesis metabolites filamentous fungi. To describe ongoing processes, model "piano regulation" proposed, whereby pressing certain key (signal) leads extraction sound "musical instrument cell", expressed production specific metabolite.

Language: Английский

Citations

18

Mechanisms of probiotic Bacillus against enteric bacterial infections DOI Creative Commons
Jiajia Zhu, Yunsheng Chen, Kálmán Imre

et al.

One Health Advances, Journal Year: 2023, Volume and Issue: 1(1)

Published: Aug. 15, 2023

Abstract Gastrointestinal infection is a leading cause of gut diseases attracting global health concerns. The emerging antimicrobial resistance in enteric pathogens drives the search viable and renewable alternatives to antibiotics for both human beings animals. Spore-forming probiotic Bacillus have received extensively interests their multiple benefits, including restoration microbiota dysbiosis reduction drug-resistant pathogens. These promising benefits are mainly attributed activity structurally diverse -derived metabolites, such as antibacterial compounds, short-chain fatty acids, other small molecules. Such metabolites show capacity directly target either individual or community bacterial pathogens, potentiate host cells microbiota. better understanding mechanisms by which modulate metabolism hosts will advance screening development . In this review, we discuss interaction among , host, summarize Bacillus- derived that act key players interactions, shedding light on mechanistic against infections.

Language: Английский

Citations

18