Metformin: update on mechanisms of action and repurposing potential

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(8), P. 460 - 476

Published: May 2, 2023

Language: Английский

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Next-generation hybrid technologies for the treatment of pharmaceutical industry effluents

Journal of Environmental Management, Journal Year: 2024, Volume and Issue: 353, P. 120197 - 120197

Published: Feb. 1, 2024

Language: Английский

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Dinickel enzyme evolved to metabolize the pharmaceutical metformin and its implications for wastewater and human microbiomes

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(10)

Published: Feb. 26, 2024

Metformin is the first-line treatment for type II diabetes patients and a pervasive pollutant with more than 180 million kg ingested globally entering wastewater. The drug's direct mode of action currently unknown but linked to effects on gut microbiomes may involve specific microbial reactions drug. In wastewater plants, metformin known be transformed by microbes guanylurea, although genes encoding this metabolism had not been elucidated. present study, we revealed function two responsible decomposition (

Language: Английский

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Transport of metformin metabolites by guanidinium exporters of the small multidrug resistance family

The Journal of General Physiology, Journal Year: 2024, Volume and Issue: 156(3)

Published: Jan. 31, 2024

Proteins from the small multidrug resistance (SMR) family are frequently associated with horizontally transferred gene arrays found in bacteria wastewater and human-adjacent biosphere. Recent studies suggest that a subset of SMR transporters might participate metabolism common pharmaceutical metformin by bacterial consortia. Here, we show both genomic plasmid-associated SMRGdx functional subtype export byproducts microbial metabolism, particularly high efficiency for guanylurea. We use solid-supported membrane electrophysiology to evaluate transport kinetics guanylurea native substrate guanidinium four representative homologs. Using an internal reference normalize independent experiments, rates comparable homologs, using proteoliposome-based assay, 2 proton:1 stoichiometry is maintained. Additional characterization properties focuses on structurally characterized homolog, Gdx-Clo, which examined pH dependence thermodynamics binding solved x-ray crystal structure bound. Together, these experiments contribute two main ways. By providing first detailed kinetic examination homolog they provide framework will inform future mechanistic this model protein. Second, study casts light potential role handling its metabolic byproducts, insight into how physiologies co-opted contend new selective pressures.

Language: Английский

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Enhanced anaerobic digestion performance and sludge filterability by membrane microaeration for anaerobic membrane bioreactor application

Bioresource Technology, Journal Year: 2024, Volume and Issue: 402, P. 130787 - 130787

Published: May 3, 2024

Language: Английский

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Insights into the action of the pharmaceutical metformin: Targeted inhibition of the gut microbial enzyme agmatinase

iScience, Journal Year: 2024, Volume and Issue: 27(2), P. 108900 - 108900

Published: Jan. 12, 2024

Metformin is the first-line treatment for type 2 diabetes, yet its mechanism of action not fully understood. Recent studies suggest metformin's interactions with gut microbiota are responsible exerting therapeutic effects. In this study, we report that metformin targets microbial enzyme agmatinase, as a competitive inhibitor, which may impair agmatine catabolism. The inhibition constant (K

Language: Английский

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Ultrastable Cobalt-Based Chainmail Catalyst for Degradation of Emerging Contaminants in Water

Applied Catalysis B Environment and Energy, Journal Year: 2024, Volume and Issue: unknown, P. 124768 - 124768

Published: Oct. 1, 2024

Language: Английский

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The universal accumulation of p-aminophenol during the microbial degradation of analgesic and antipyretic acetaminophen in WWTPs: a novel metagenomic perspective

Microbiome, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 7, 2025

Abstract Background Acetaminophen, a widely used analgesic and antipyretic drug, has become significant aquatic micro-pollutant due to its extensive global production increased consumption, particularly during the COVID-19 pandemic. Its high-water solubility leads pervasive presence in wastewater treatment plants (WWTPs), posing substantial risks environment human health. Biological is one of promising approaches remove such pollutants. Although previous studies have isolated acetaminophen-degrading pure cultures proposed catabolic pathways, interactions between microbiotas acetaminophen, distribution feature acetaminophen degradation genes, gene-driven fate real-world remain largely unexplored. Results Among water samples from 20 WWTPs across China, was detected 19 at concentrations ranging 0.06 29.20 nM. However, p -aminophenol, more toxic metabolite, all significantly higher (23.93 108.68 nM), indicating bottleneck WWTPs. Metagenomic analysis both above datasets revealed consistently abundance initial amidases compared downstream enzymes, potentially having explained reason for bottleneck. Meanwhile, close correlation Actinomycetota by genome-based taxonomy suggests species-dependent pattern. Additionally, distinct amidase ApaA characterized newly Rhodococcus sp. NyZ502 (Actinomycetota), represents predominant category Significant phylogenetic structural diversity observed among putative suggest versatile hydrolysis potential Conclusions This study enhances our understanding acetaminophen’s environmental highlights possible occurrence ecological driven imbalanced genes process

Language: Английский

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Discovery of a Ni2+-dependent heterohexameric metformin hydrolase

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

Published: July 20, 2024

The biguanide drug metformin is a first-line blood glucose-lowering medication for type 2 diabetes, leading to its presence in the global environment. However, little known about fate of by microbial catabolism. Here, we characterize Ni

Language: Английский

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Microbial degradation of contaminants of emerging concern: metabolic, genetic and omics insights for enhanced bioremediation

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 19, 2024

The perpetual release of natural/synthetic pollutants into the environment poses major risks to ecological balance and human health. Amongst these, contaminants emerging concern (CECs) are characterized by their recent introduction/detection in various niches, thereby causing significant hazards necessitating removal. Pharmaceuticals, plasticizers, cyanotoxins pesticides groups CECs that highly toxic found occur compartments biosphere. sources these compounds can be multipartite including industrial discharge, improper disposal, excretion unmetabolized residues, eutrophication etc ., while fate persistence determined factors such as physico-chemical properties, environmental conditions, biodegradability hydrological factors. resultant exposure microbiota has imposed a selection pressure resulted evolution metabolic pathways for biotransformation and/or utilization sole source carbon energy. Such microbial degradation phenotype exploited clean-up from environment, offering cost-effective eco-friendly alternative abiotic methods removal, mitigating toxicity. However, efficient bioprocess development bioremediation strategies requires extensive understanding individual components pathway gene clusters, proteins/enzymes, metabolites associated regulatory mechanisms. “Omics” “Meta-omics” techniques aid providing crucial insights complex interactions functions well community, enabling more effective targeted bioremediation. Aside natural isolates, engineering approaches employ application genetic enhance diversity rates. integration omics data will further developing systemic-level strategies, optimising process. This review describes bacterial catabolic pathways, genetics, four CECs: pharmaceuticals, cyanotoxins, pesticides.

Language: Английский

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