基于合成受体的食品污染物生物检测进展

doi:10.12211/2096-8280.2021-048

合成生物学 ›› 2022, Vol. 3 ›› Issue (2): 399-414.DOI: 10.12211/2096-8280.2021-048

基于合成受体的食品污染物生物检测进展

胥欣欣¹^,², 匡华¹^,²

^1.江南大学食品科学技术国家重点实验室，江苏无锡 214122
^2.江南大学食品学院，生物界面与生物检测研究所，江苏无锡 214122

收稿日期:2021-04-21 修回日期:2021-09-13 出版日期:2022-04-30 发布日期:2022-05-11
通讯作者: 匡华
作者简介:胥欣欣（1989—），男，博士，博士后研究员。研究方向为功能性生物大分子蛋白的规模化制备及应用。 E-mail：xuxinxin@jiangnan.edu.cn
匡华（1981—），女，博士，教授，主要从事食品中危害物质快速检测和手性纳米生物探针构建等工作。研究方向包括单克隆抗体和重组受体开发、分子识别、信号放大与传感新策略。 E-mail：kuangh@jiangnan.edu.cn
基金资助:
国家重点研发计划(2018YFC1602303)

Advances in the biological detection of food contaminants based on synthetic receptors

Xinxin XU¹^,², Hua KUANG¹^,²

^1.State Key Laboratory of Food Science and Technology，Jiangnan University，Wuxi 214122，Jiangsu，China
^2.International Joint Research Laboratory for Biointerface and Biodetection，and School of Food Science and Technology，Jiangnan University，Wuxi，214122，Jiangsu，China

Received:2021-04-21 Revised:2021-09-13 Online:2022-04-30 Published:2022-05-11
Contact: Hua KUANG

摘要/Abstract

摘要：

在细胞生物学中，受体是指在细胞表面或细胞内任何能够与激素、药物、信号分子等配体结合，从而引起细胞功能变化的生物大分子。随着生物学的快速发展，各种天然的、非天然的化合物在细胞中的识别、转运等信号通路及分子作用机制已被逐渐解析。酶、离子通道、转运蛋白等生物靶标都可以归类为广义上的受体。类似于抗体-抗原，受体-配体反应同样具有高亲和力、高特异性和高饱和，在食品安全快速检测领域有一定的发展潜力。受体蛋白的定向进化设计、潜在受体的开发利用以及多学科技术的交叉互融是受体生物传感分析方法发展的巨大推动力。本文简单介绍了受体的分类以及受体-配体的关系，概述了合成生物学中不同底盘生物对受体蛋白量产化的偏好性，回顾了基于受体蛋白的筛查分析方法在食品安全检测相关领域的研究进展，如抗生素残留、农药残留、非法使用添加剂、生物毒素及生物性污染等。最后，探讨了受体结合测定法的优缺点，分析了目前基于受体的分析方法所面临的瓶颈问题和可能的解决方式，展望了合成受体在食品安全检测应用领域中的发展方向。

关键词: 合成生物学, 受体蛋白, 食品安全, 污染物, 检测分析

Abstract:

In cell biology, receptors are biological macromolecules that can bind to hormones, drugs, signaling molecules, and other ligands inside cells or on their surfaces, thereby causing changes in the functions of these cells. With the rapid development of biology, signal pathways and molecular mechanisms, such as the recognition and transport of various natural and unnatural compounds in cells, have been gradually elucidated. Biological targets, for example, enzymes, ion channels and transporters, can be classified as receptors in a broad sense. Similar to antibody-antigen, the receptor-ligand binding also shows high affinity, specificity and saturation, leading to its potential applications in the fast detection for food safety. Here, we briefly introduce the classification of receptors and the relationship between receptors and ligands. The preparations of receptor proteins, including the selection of chassis organisms such as E. coli, yeast, insect cells and mammalian cells for protein mass production, the utilization of cell-free translational systems, the process of protein expression and functional improvement, are also summarized. The main topic of this article is to review the research progress of receptor-based screening and analytical methods in fast detection for food safety, such as antibiotic residues, pesticide residues, illegal use of additives, biotoxins and biological pollutants. In addition, we also discuss the advantages and disadvantages of receptor-binding assays compared to antibody-based analytic methods, and highlight the current bottlenecks for the receptor-binding assay and possible solutions. Finally, we prospect the development of synthetic receptors in the application for food safety assurance. The directed evolution of receptor proteins that is based on rational design, the further exploitation and wide utilization of potential receptors, and the combination of multidisciplinary technologies will provide a driving force for the development and promotion of the receptor-based analytical methods. Such methods have great potential, and will be used in research or for commercial purpose accordingly.

Key words: synthetic biology, receptor protein, food safety, contaminant, detection and analysis

中图分类号:

TS 207.3

胥欣欣, 匡华. 基于合成受体的食品污染物生物检测进展[J]. 合成生物学, 2022, 3(2): 399-414.

Xinxin XU, Hua KUANG. Advances in the biological detection of food contaminants based on synthetic receptors[J]. Synthetic Biology Journal, 2022, 3(2): 399-414.

图/表 5

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表达系统	优势	劣势
原核表达系统	操作简单，培养周期短，成本低廉，表达量高	无翻译后修饰，易形成包含体
酵母表达系统	遗传背景清楚，操作简单，培养周期短，成本低廉，表达量高，无内毒素污染，简单的翻译后修饰	糖基化修饰与天然蛋白有差异
哺乳动物表达系统	糖基化修饰完整，蛋白折叠正确、活性高，最接近天然蛋白	周期长，产率低，耗费高
昆虫表达系统	翻译后修饰系统比原核和酵母系统更加完善，生产周期比哺乳动物系统短，重组蛋白产量高	病毒侵染导致细胞死亡，可能使得蛋白修饰不完整；糖基化修饰与天然蛋白有差异

表达系统	优势	劣势
原核表达系统	操作简单，培养周期短，成本低廉，表达量高	无翻译后修饰，易形成包含体
酵母表达系统	遗传背景清楚，操作简单，培养周期短，成本低廉，表达量高，无内毒素污染，简单的翻译后修饰	糖基化修饰与天然蛋白有差异
哺乳动物表达系统	糖基化修饰完整，蛋白折叠正确、活性高，最接近天然蛋白	周期长，产率低，耗费高
昆虫表达系统	翻译后修饰系统比原核和酵母系统更加完善，生产周期比哺乳动物系统短，重组蛋白产量高	病毒侵染导致细胞死亡，可能使得蛋白修饰不完整；糖基化修饰与天然蛋白有差异

抗生素类型	受体蛋白	检测方式	检测基质	可检测种类数	LOD/(ng/mL)	IC₅₀/(ng/mL)	参考文献
β-内酰胺类	PBP2x*	ELISA	牛奶	15	0.08～27.45	—	[21]
	sPBP3*	ELISA	PBS/牛奶	27/13	0.26～109.46/0.52～27.40	2.13～426.02	[34]
	PBP2x*	ELISA	牛奶、肉汁、鸡蛋、蜂蜜	6	—	—	[35]
	BlaR-CTD	ELISA	牛奶、牛肉、鸡肉	11	—	0.18～170.81	[22]
	BlaR-CTD	ELISA	13种食物	40	—	—	[30]
	BlaR-CTD	GICA	牛奶、鸡肉	21	低于限量要求	—	[36]
	PBP-6	SERS-LFIA	牛奶	1	0.01	1.77	[37]
磺胺类	DHPS	ELISA	牛奶	28	—	426～50 000	[20]
	DHPS-DHPPP	FPA/ELISA	牛奶	29	1.6～59/ 1.15～14.91	<100	[38-39]
	DHPS-DHPPP	ELISA	鸡肉、猪肉、鸡蛋、蜂蜜	1	5.57～23.22	—	[40]
四环素类	TetR-tetO	ELISA	牛奶、牛血清	8	0.1～7.2	—	[41]
	TetR-tetO	试纸条法	牛奶、肉末、牛血清	8	—	—	[42]
	TetR	CL-ELISA	牛奶	5	0.005～0.016	0.5～2.2	[43]
	TetR	ELISA	鸡蛋	9	0.3～5.8	3.1～17.2	[31]
	TetR-tetO	化学发光微流控条	自来水	1	0.1	—	[44]
大环内酯类	MphR(A)	细胞传感器	—	1	—	—	[45]
	MphR(A)	微生物传感器	—	1	—	—	[46]
	MphR(A)	ELISA	牛奶、牛血清	5	1.7～5000	—	[41]
	MphR(A)、MphR(E)	ELISA	原奶	1	—	—	[47-48]

抗生素类型	受体蛋白	检测方式	检测基质	可检测种类数	LOD/(ng/mL)	IC₅₀/(ng/mL)	参考文献
β-内酰胺类	PBP2x*	ELISA	牛奶	15	0.08～27.45	—	[21]
	sPBP3*	ELISA	PBS/牛奶	27/13	0.26～109.46/0.52～27.40	2.13～426.02	[34]
	PBP2x*	ELISA	牛奶、肉汁、鸡蛋、蜂蜜	6	—	—	[35]
	BlaR-CTD	ELISA	牛奶、牛肉、鸡肉	11	—	0.18～170.81	[22]
	BlaR-CTD	ELISA	13种食物	40	—	—	[30]
	BlaR-CTD	GICA	牛奶、鸡肉	21	低于限量要求	—	[36]
	PBP-6	SERS-LFIA	牛奶	1	0.01	1.77	[37]
磺胺类	DHPS	ELISA	牛奶	28	—	426～50 000	[20]
	DHPS-DHPPP	FPA/ELISA	牛奶	29	1.6～59/ 1.15～14.91	<100	[38-39]
	DHPS-DHPPP	ELISA	鸡肉、猪肉、鸡蛋、蜂蜜	1	5.57～23.22	—	[40]
四环素类	TetR-tetO	ELISA	牛奶、牛血清	8	0.1～7.2	—	[41]
	TetR-tetO	试纸条法	牛奶、肉末、牛血清	8	—	—	[42]
	TetR	CL-ELISA	牛奶	5	0.005～0.016	0.5～2.2	[43]
	TetR	ELISA	鸡蛋	9	0.3～5.8	3.1～17.2	[31]
	TetR-tetO	化学发光微流控条	自来水	1	0.1	—	[44]
大环内酯类	MphR(A)	细胞传感器	—	1	—	—	[45]
	MphR(A)	微生物传感器	—	1	—	—	[46]
	MphR(A)	ELISA	牛奶、牛血清	5	1.7～5000	—	[41]
	MphR(A)、MphR(E)	ELISA	原奶	1	—	—	[47-48]

非法添加剂类型	受体蛋白	检测方式	检测基质	LOD/(ng/mL)	IC₅₀/(ng/mL)	参考文献
β兴奋剂	β兴奋剂受体	ELISA	药片	—	—	[51]
	β2-AR	ELRA	猪尿	—	34～63	[23]
	β2-AR	ELRA	猪尿	—	45.99～78.02	[25]
	β2-AR	ELRA	猪尿	—	28.36～59.57	[24]
	β2-AR	ELRA	—	5.20	30.38	[52]
PDE5抑制剂	磷酸二酯酶PDE5	荧光检测方法	膳食补充剂	—	0.4～4.0	[56]

基于合成受体的食品污染物生物检测进展

Advances in the biological detection of food contaminants based on synthetic receptors

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