Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences

Abstract Carboxylesterases, historically referred as non-specific esterases, are ubiquitous hydrolases with high catalytic efficiency. Without exceptions, all mammalian species studied contain multiple forms of carboxylesterases. While having been widely studied in humans and experimental animals, t...

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Autores principales: Qiongqiong Zhou, Qiling Xiao, Yongliang Zhang, Xiliang Wang, Yuncai Xiao, Deshi Shi
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Publicado: Nature Portfolio 2019
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Acceso en línea:https://doaj.org/article/82312403508a4f7d9b272cb3a586f319
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spelling oai:doaj.org-article:82312403508a4f7d9b272cb3a586f3192021-12-02T15:09:28ZPig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences10.1038/s41598-019-51580-42045-2322https://doaj.org/article/82312403508a4f7d9b272cb3a586f3192019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51580-4https://doaj.org/toc/2045-2322Abstract Carboxylesterases, historically referred as non-specific esterases, are ubiquitous hydrolases with high catalytic efficiency. Without exceptions, all mammalian species studied contain multiple forms of carboxylesterases. While having been widely studied in humans and experimental animals, these enzymes remain to be characterized in farm animals. In this study, we showed that pig liver esterase 1 (PLE1) and pig liver esterase 6 (PLE6) were highly active toward amoxicillin (AMO) and ampicillin (AMP), two major antibiotics that are widely used in food-supplements. Mass-spectrometric analysis established that the hydrolysis occurred at the β-lactam amide bond and the hydrolysis drastically decreased or completely eliminated the antibacterial activity. Furthermore, hydrolytic activity and proteomic analysis suggested that trace PLEs existed in pig plasma and contributed little to the hydrolysis of AMO and AMP. These results suggested that carboxylesterases-based hydrolysis determines the therapeutic intensity of these and related antibiotics and the magnitude of the determination occurs in a species-dependent manner.Qiongqiong ZhouQiling XiaoYongliang ZhangXiliang WangYuncai XiaoDeshi ShiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Qiongqiong Zhou
Qiling Xiao
Yongliang Zhang
Xiliang Wang
Yuncai Xiao
Deshi Shi
Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences
description Abstract Carboxylesterases, historically referred as non-specific esterases, are ubiquitous hydrolases with high catalytic efficiency. Without exceptions, all mammalian species studied contain multiple forms of carboxylesterases. While having been widely studied in humans and experimental animals, these enzymes remain to be characterized in farm animals. In this study, we showed that pig liver esterase 1 (PLE1) and pig liver esterase 6 (PLE6) were highly active toward amoxicillin (AMO) and ampicillin (AMP), two major antibiotics that are widely used in food-supplements. Mass-spectrometric analysis established that the hydrolysis occurred at the β-lactam amide bond and the hydrolysis drastically decreased or completely eliminated the antibacterial activity. Furthermore, hydrolytic activity and proteomic analysis suggested that trace PLEs existed in pig plasma and contributed little to the hydrolysis of AMO and AMP. These results suggested that carboxylesterases-based hydrolysis determines the therapeutic intensity of these and related antibiotics and the magnitude of the determination occurs in a species-dependent manner.
format article
author Qiongqiong Zhou
Qiling Xiao
Yongliang Zhang
Xiliang Wang
Yuncai Xiao
Deshi Shi
author_facet Qiongqiong Zhou
Qiling Xiao
Yongliang Zhang
Xiliang Wang
Yuncai Xiao
Deshi Shi
author_sort Qiongqiong Zhou
title Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences
title_short Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences
title_full Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences
title_fullStr Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences
title_full_unstemmed Pig liver esterases PLE1 and PLE6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences
title_sort pig liver esterases ple1 and ple6: heterologous expression, hydrolysis of common antibiotics and pharmacological consequences
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/82312403508a4f7d9b272cb3a586f319
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AT qilingxiao pigliveresterasesple1andple6heterologousexpressionhydrolysisofcommonantibioticsandpharmacologicalconsequences
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