Epiberberine: a potential rumen microbial urease inhibitor to reduce ammonia release screened by targeting UreG

文献类型： 外文期刊

第一作者： Zhang, Xiaoyin

作者： Zhang, Xiaoyin;Xiong, Zhanbo;He, Yue;Zheng, Nan;Zhao, Shengguo;Wang, Jiaqi

作者机构：

关键词： Urease inhibitor; Epiberberine; UreG; Nitrogen emission; Rumen

期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：5.0； 五年影响因子：5.2 ）

ISSN： 0175-7598

年卷期： 2024 年 108 卷 1 期

页码：

收录情况： SCI

摘要： Rumen microbial urease inhibitors have been proposed for regulating nitrogen emission and improving nitrogen utilization efficiency in ruminant livestock industry. However, studies on plant-derived natural inhibitors of rumen microbial urease are limited. Urease accessory protein UreG, plays a crucial role in facilitating urease maturation, is a new target for design of urease inhibitor. The objective of this study was to select the potential effective inhibitor of rumen microbial urease from major protoberberine alkaloids in Rhizoma Coptidis by targeting UreG. Our results showed that berberine chloride and epiberberine exerted superior inhibition potential than other alkaloids based on GTPase activity study of UreG. Berberine chloride inhibition of UreG was mixed type, while inhibition kinetics type of epiberberine was uncompetitive. Furthermore, epiberberine was found to be more effective than berberine chloride in inhibiting the combination of nickel towards UreG and inducing changes in the second structure of UreG. Molecular modeling provided the rational structural basis for the higher inhibition potential of epiberberine, amino acid residues in G1 motif and G3 motif of UreG formed interactions with D ring of berberine chloride, while interacted with A ring and D ring of epiberberine. We further demonstrated the efficacy of epiberberine in the ruminal microbial fermentation with low ammonia release and urea degradation. In conclusion, our study clearly indicates that epiberberine is a promising candidate as a safe and effective inhibitor of rumen microbial urease and provides an optimal strategy and suitable feed additive for regulating nitrogen excretion in ruminants in the future.

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