State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
Key Laboratory of Development of Veterinary Diagnostic Products of Ministry of Agricultural, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.
Sci Rep. 2019 Oct 29;9(1):15564. doi: 10.1038/s41598-019-51580-4.
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.
羧酯酶，历史上也被称为非特异性酯酶，是一种广泛存在的水解酶，具有很高的催化效率。无一例外，所有研究过的哺乳动物物种都含有多种形式的羧酯酶。虽然这些酶在人类和实验动物中得到了广泛的研究，但在农场动物中仍有待于进行特征描述。在这项研究中，我们表明猪肝酯酶 1（PLE1）和猪肝酯酶 6（PLE6）对阿莫西林（AMO）和氨苄西林（AMP）两种广泛应用于食品补充剂的主要抗生素具有很高的活性。质谱分析确定了水解发生在β-内酰胺酰胺键上，水解大大降低或完全消除了抗菌活性。此外，水解活性和蛋白质组学分析表明，痕量的 PLE 存在于猪血浆中，对 AMO 和 AMP 的水解贡献很小。这些结果表明，基于羧酯酶的水解决定了这些和相关抗生素的治疗强度，而这种决定的程度以物种依赖的方式发生。
