A prescription for engineering PFAS biodegradation DOI Creative Commons

Lawrence P. Wackett,

Serina L. Robinson

Biochemical Journal, Journal Year: 2024, Volume and Issue: 481(23), P. 1757 - 1770

Published: Nov. 25, 2024

Per- and polyfluorinated chemicals (PFAS) are of rising concern due to environmental persistence emerging evidence health risks humans. Environmental is largely attributed a failure microbes degrade PFAS. PFAS recalcitrance has been proposed result from chemistry, specifically C-F bond strength, or biology, negative selection fluoride toxicity. Given natural evolution many hurdles, this review advocates for strategy laboratory engineering evolution. Enzymes identified participate in defluorination reactions have discovered all Enzyme Commission classes, providing palette metabolic engineering. In vivo biodegradation will require multiple types powerful mitigation mechanisms act concert. The necessary steps to: (1) engineer bacteria that survive very high, unnatural levels fluoride, (2) design, evolve, screen enzymes cleave C–F bonds broader array substrates, (3) create overall physiological conditions make positive selective pressure with substrates.

Language: Английский

Insights into the action of the pharmaceutical metformin: Targeted inhibition of the gut microbial enzyme agmatinase DOI Creative Commons
Lambros J. Tassoulas,

Lawrence P. Wackett

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

Citations

4
Adaptation towards catabolic biodegradation of trace organic contaminants in activated sludge DOI Creative Commons

Carolin Seller-Brison,

Antoine Brison, Yaochun Yu

et al.

Water Research, Journal Year: 2024, Volume and Issue: 266, P. 122431 - 122431

Published: Sept. 11, 2024

Trace organic contaminants (TrOCs) are omnipresent in wastewater treatment plants (WWTPs), yet, their removal during is oftentimes incomplete and underlying biotransformation mechanisms not fully understood. In this study, we elucidate how different factors, including pre-exposure levels duration, influence microbial adaptation towards catabolic TrOC biodegradation its potential role biological treatment. Four sequencing batch reactors (SBRs) were operated parallel three succeeding phases, adding removing a selection of 26 TrOCs at concentration levels. After each phase SBR operation, series experiments was conducted to monitor kinetics those same across various spike concentrations. For half our test TrOCs, detected increased sludge pre-exposed concentrations ≥5 µg L

Language: Английский

Citations

4
Discovery of a Ni2+-dependent heterohexameric metformin hydrolase DOI Creative Commons
Tao Li,

Zhi-Jing Xu,

Shuting Zhang

et al.

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

Citations

3
Metformin hydrolase is a recently evolved nickel-dependent heteromeric ureohydrolase DOI Creative Commons
Malte Sinn,

Lea Riede,

Jennifer R. Fleming

et al.

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

Published: Sept. 13, 2024

Abstract The anti-diabetic drug metformin is one of the most widely prescribed medicines in world. Together with its degradation product guanylurea, it a major pharmaceutical pollutant wastewater treatment plants and surface waters. An operon comprising two genes ureohydrolase family Pseudomonas Aminobacter species has recently been implicated degradation. However, corresponding proteins have not characterized. Here we show that these encode Ni 2+ -dependent enzyme efficiently specifically hydrolyzes to guanylurea dimethylamine. active heteromeric complex α- β- subunits which only α-subunits contain conserved His Asp residues for coordination ions site. A crystal structure hydrolase reveals an α 2 β 4 stoichiometry hexameric complex, unprecedented family. By studying closely related but more distributed enzyme, find putative predecessor dimethylguanidine instead metformin. Our findings establish molecular basis hydrolysis as primary pathway biodegradation provide insight into recent evolution response anthropogenic compound.

Language: Английский

Citations

1
Biochemical and genomic evidence for converging metabolic routes of metformin and biguanide breakdown in environmental Pseudomonads DOI Creative Commons

Katie B. Wissbroecker,

Anthony J. Zmuda,

Harsheeth Karumanchi

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107935 - 107935

Published: Oct. 1, 2024

Language: Английский

Citations

1
One his, two his…the emerging roles of histidine in cellular nickel trafficking DOI
Peter T. Chivers, Priyanka Basak, Michael J. Maroney

et al.

Journal of Inorganic Biochemistry, Journal Year: 2024, Volume and Issue: 259, P. 112668 - 112668

Published: July 17, 2024

Language: Английский

Citations

1
A prescription for engineering PFAS biodegradation DOI Creative Commons

Lawrence P. Wackett,

Serina L. Robinson

Biochemical Journal, Journal Year: 2024, Volume and Issue: 481(23), P. 1757 - 1770

Published: Nov. 25, 2024

Per- and polyfluorinated chemicals (PFAS) are of rising concern due to environmental persistence emerging evidence health risks humans. Environmental is largely attributed a failure microbes degrade PFAS. PFAS recalcitrance has been proposed result from chemistry, specifically C-F bond strength, or biology, negative selection fluoride toxicity. Given natural evolution many hurdles, this review advocates for strategy laboratory engineering evolution. Enzymes identified participate in defluorination reactions have discovered all Enzyme Commission classes, providing palette metabolic engineering. In vivo biodegradation will require multiple types powerful mitigation mechanisms act concert. The necessary steps to: (1) engineer bacteria that survive very high, unnatural levels fluoride, (2) design, evolve, screen enzymes cleave C–F bonds broader array substrates, (3) create overall physiological conditions make positive selective pressure with substrates.

Language: Английский

Citations

0