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组合蛋白质纳米生物催化剂对混合物中霉菌毒素的降解:计算机模拟、体外和体内研究

Degradation of mycotoxins in mixtures by combined proteinous nanobiocatalysts: In silico, in vitro and in vivo.

作者信息

Lyagin Ilya, Maslova Olga, Stepanov Nikolay, Efremenko Elena

机构信息

Faculty of Chemistry, Lomonosov Moscow State University, Lenin Hills 1/3, 119991 Moscow, Russia.

Faculty of Chemistry, Lomonosov Moscow State University, Lenin Hills 1/3, 119991 Moscow, Russia.

出版信息

Int J Biol Macromol. 2022 Oct 1;218:866-877. doi: 10.1016/j.ijbiomac.2022.07.179. Epub 2022 Jul 28.

Abstract

New combined proteinous (enzymatic) nanobiocatalysts capable of destructing mycotoxins in mixtures were developed and investigated in vitro and in vivo. Candidate enzymes for such combined biocatalysts were computationally screened using molecular docking of mycotoxins to the proteins. Catalytic characteristics of the 7 selected enzymes were estimated in the potential reactions with various mycotoxins (aflatoxin B, citrinin, deoxynivalenol, ergotamine, fumonisin B, gliotoxin, ochratoxin A, patulin, sterigmatocystin, T-2 toxin, zearalenone) at different pH values. To stabilize the enzymes hydrolyzing the mycotoxins, special biopolymers were selected using computer modeling. The poly(glutamic acid) was revealed as universal partner for the polyelectrolyte complexes with the selected enzymes. Finally, Sprague-Dawley rats were used for in vivo feeding experiments with feed contaminated by mycotoxin mixture at doses being up to orders of magnitude higher than maximum allowable limits. The treatment of contaminated feed by novel combined enzyme nanocomplexes significantly decreased negative effects of mycotoxin mixture on blood biochemical parameters which indicated huge damage to liver and kidneys of intoxicated animals. Such nanobiocatalysts and enzymatic treatment itself seem to be promising way for ensuring both food and feed chemical safety.

摘要

开发了能够在混合物中破坏霉菌毒素的新型复合蛋白质(酶)纳米生物催化剂,并在体外和体内进行了研究。通过霉菌毒素与蛋白质的分子对接,对这类复合生物催化剂的候选酶进行了计算筛选。在不同pH值下,对7种选定酶与各种霉菌毒素(黄曲霉毒素B、桔霉素、脱氧雪腐镰刀菌烯醇、麦角胺、伏马菌素B、 gliotoxin、赭曲霉毒素A、棒曲霉素、柄曲霉素、T-2毒素、玉米赤霉烯酮)潜在反应的催化特性进行了评估。为了稳定水解霉菌毒素的酶,通过计算机建模选择了特殊的生物聚合物。发现聚谷氨酸是与选定酶形成聚电解质复合物的通用伙伴。最后,使用斯普拉格-道利大鼠进行体内喂养实验,所用饲料被霉菌毒素混合物污染,剂量比最大允许限量高出几个数量级。用新型复合酶纳米复合物处理受污染的饲料,显著降低了霉菌毒素混合物对血液生化参数的负面影响,这些参数表明中毒动物的肝脏和肾脏受到了巨大损害。这种纳米生物催化剂及其酶处理本身似乎是确保食品和饲料化学安全的有前途的方法。

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