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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2019
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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) |
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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 |
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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 |
work_keys_str_mv |
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