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

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 enzy...

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Bibliographic Details
Published in:Scientific reports 2019-10, Vol.9 (1), p.15564-12, Article 15564
Main Authors: Zhou, Qiongqiong, Xiao, Qiling, Zhang, Yongliang, Wang, Xiliang, Xiao, Yuncai, Shi, Deshi
Format: Article
Language:English
Subjects:
13/1
38/109
38/77
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692/4017
82/29
82/58
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82/83
Amoxicillin
Amoxicillin - chemistry
Amoxicillin - pharmacology
Ampicillin
Ampicillin - chemistry
Ampicillin - pharmacology
Animals
Anti-Bacterial Agents - pharmacology
Antibacterial activity
Antibiotics
beta-Lactams
Carboxylesterase - genetics
Catalysis
Dietary supplements
Esterase
Humanities and Social Sciences
Humans
Hydrolysis
Hydrolysis - drug effects
Liver
Liver - drug effects
Liver - enzymology
multidisciplinary
Proteomics
Science
Science (multidisciplinary)
Swine
β-Lactam antibiotics
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-51580-4