Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products

Metformin is used globally to treat type II diabetes, has demonstrated anti-ageing and COVID mitigation effects and is a major anthropogenic pollutant to be bioremediated by wastewater treatment plants (WWTPs). Metformin is not adsorbed well by activated carbon and toxic N-chloro derivatives can for...

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Main Authors: Betsy M. Martinez-Vaz, Anthony G. Dodge, Rachael M. Lucero, Randy B. Stockbridge, Ashley A. Robinson, Lambros J. Tassoulas, Lawrence P. Wackett
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.1086261/full
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author Betsy M. Martinez-Vaz
Anthony G. Dodge
Rachael M. Lucero
Randy B. Stockbridge
Ashley A. Robinson
Lambros J. Tassoulas
Lawrence P. Wackett
author_facet Betsy M. Martinez-Vaz
Anthony G. Dodge
Rachael M. Lucero
Randy B. Stockbridge
Ashley A. Robinson
Lambros J. Tassoulas
Lawrence P. Wackett
author_sort Betsy M. Martinez-Vaz
collection DOAJ
description Metformin is used globally to treat type II diabetes, has demonstrated anti-ageing and COVID mitigation effects and is a major anthropogenic pollutant to be bioremediated by wastewater treatment plants (WWTPs). Metformin is not adsorbed well by activated carbon and toxic N-chloro derivatives can form in chlorinated water. Most earlier studies on metformin biodegradation have used wastewater consortia and details of the genomes, relevant genes, metabolic products, and potential for horizontal gene transfer are lacking. Here, two metformin-biodegrading bacteria from a WWTP were isolated and their biodegradation characterized. Aminobacter sp. MET metabolized metformin stoichiometrically to guanylurea, an intermediate known to accumulate in some environments including WWTPs. Pseudomonasmendocina MET completely metabolized metformin and utilized all the nitrogen atoms for growth. Pseudomonas mendocina MET also metabolized metformin breakdown products sometimes observed in WWTPs: 1-N-methylbiguanide, biguanide, guanylurea, and guanidine. The genome of each bacterium was obtained. Genes involved in the transport of guanylurea in Aminobacter sp. MET were expressed heterologously and shown to serve as an antiporter to expel the toxic guanidinium compound. A novel guanylurea hydrolase enzyme was identified in Pseudomonas mendocina MET, purified, and characterized. The Aminobacter and Pseudomonas each contained one plasmid of 160 kb and 90 kb, respectively. In total, these studies are significant for the bioremediation of a major pollutant in WWTPs today.
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spelling doaj.art-08c30f104ea544edbdd067c7cd19b32b2022-12-22T04:22:37ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-12-011010.3389/fbioe.2022.10862611086261Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and productsBetsy M. Martinez-Vaz0Anthony G. Dodge1Rachael M. Lucero2Randy B. Stockbridge3Ashley A. Robinson4Lambros J. Tassoulas5Lawrence P. Wackett6Department of Biology and Biochemistry Program, Hamline University, St. Paul, MN, United StatesDepartment of Biochemistry, Molecular Biology and Biophysics and BioTechnology Institute, University of Minnesota, St. Paul, MN, United StatesProgram in Chemical Biology and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, United StatesProgram in Chemical Biology and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, United StatesDepartment of Biology and Biochemistry Program, Hamline University, St. Paul, MN, United StatesDepartment of Biochemistry, Molecular Biology and Biophysics and BioTechnology Institute, University of Minnesota, St. Paul, MN, United StatesDepartment of Biochemistry, Molecular Biology and Biophysics and BioTechnology Institute, University of Minnesota, St. Paul, MN, United StatesMetformin is used globally to treat type II diabetes, has demonstrated anti-ageing and COVID mitigation effects and is a major anthropogenic pollutant to be bioremediated by wastewater treatment plants (WWTPs). Metformin is not adsorbed well by activated carbon and toxic N-chloro derivatives can form in chlorinated water. Most earlier studies on metformin biodegradation have used wastewater consortia and details of the genomes, relevant genes, metabolic products, and potential for horizontal gene transfer are lacking. Here, two metformin-biodegrading bacteria from a WWTP were isolated and their biodegradation characterized. Aminobacter sp. MET metabolized metformin stoichiometrically to guanylurea, an intermediate known to accumulate in some environments including WWTPs. Pseudomonasmendocina MET completely metabolized metformin and utilized all the nitrogen atoms for growth. Pseudomonas mendocina MET also metabolized metformin breakdown products sometimes observed in WWTPs: 1-N-methylbiguanide, biguanide, guanylurea, and guanidine. The genome of each bacterium was obtained. Genes involved in the transport of guanylurea in Aminobacter sp. MET were expressed heterologously and shown to serve as an antiporter to expel the toxic guanidinium compound. A novel guanylurea hydrolase enzyme was identified in Pseudomonas mendocina MET, purified, and characterized. The Aminobacter and Pseudomonas each contained one plasmid of 160 kb and 90 kb, respectively. In total, these studies are significant for the bioremediation of a major pollutant in WWTPs today.https://www.frontiersin.org/articles/10.3389/fbioe.2022.1086261/fullmetforminAminobacterPseudomonasgenomesplasmidsguanylurea
spellingShingle Betsy M. Martinez-Vaz
Anthony G. Dodge
Rachael M. Lucero
Randy B. Stockbridge
Ashley A. Robinson
Lambros J. Tassoulas
Lawrence P. Wackett
Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products
Frontiers in Bioengineering and Biotechnology
metformin
Aminobacter
Pseudomonas
genomes
plasmids
guanylurea
title Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products
title_full Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products
title_fullStr Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products
title_full_unstemmed Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products
title_short Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products
title_sort wastewater bacteria remediating the pharmaceutical metformin genomes plasmids and products
topic metformin
Aminobacter
Pseudomonas
genomes
plasmids
guanylurea
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.1086261/full
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AT ashleyarobinson wastewaterbacteriaremediatingthepharmaceuticalmetformingenomesplasmidsandproducts
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