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一种对抗植物病原真菌的工程化多结构域抗真菌多肽

丘小庆, 仝崇毅, 钟真麒, 王万琪, 左越文, 黄云, 张璐, 张向利, 张红霞, 李荣旗, 王晶, 陈昊, 李芸芸, George Wu, 王和

四川大学华西医院生物膜及膜蛋白实验室；华西第二医院遗传实验室，成都 610041；成都中医药大学病理科，成都 610072；四川雅安市雨城区农业局植保站，雅安 625000；四川农业大学植物保护系，雅安 625000；北京科润维德生物技术有限公司，北京 100080；美国康涅狄格州立大学医学中心胃肠病学系，法明顿 06030，美国

摘要

真菌病原体已成为危害人类健康和农业的主要难题。作为一类真核细胞，真菌某些重要的生物特性与哺乳类动物的细胞雷同，以致现有的抗真菌抗生素往往不能区分真菌细胞和哺乳类动物细胞，导致严重的毒副作用。因此急需开发既有效、又安全的新型抗真菌药物。E1族大肠菌素是大肠杆菌产生的一种可形成离子通道的细菌素，它们只能杀伤大肠杆菌及亲缘关系接近的某些细菌。我们应用生物工程技术将白色念珠菌α交配信息素连接在大肠菌素Ia通道结构域上，即构成一种新型融合蛋白——信息菌素-CA (PMC-CA)。间接荧光标记数据显示该信息菌素可结合在真菌细胞上，实验室/田间实验数据证实信息菌素可抑制真菌生长。按分子量标化，田间实验数据证实信息菌素对稻瘟病的保护率显著高于三唑类、三环唑和稻瘟灵等现用抗稻瘟病药物的保护率。上述结果提示该融合蛋白具有发展成为农业抗真菌药物的价值。

关键词： 细菌素类蛋白; 交配信息素; 融合抗真菌多肽

分类号：Q812；S435.111.4+1

An engineered multidomain fungicidal peptide against plant fungal pathogens

QIU Xiao-Qing, TONG Chong-Yi, ZHONG Zhen-Qi, WANG Wan-Qi, ZUO Yue-Wen, HUANG Yun, ZHANG Lu, ZHANG Xiang-Li, ZHANG Hong-Xia, LI Rong-Qi, WANG Jing, CHEN Hao, LI Yun-Yun, WU George, WANG He

Laboratory of Biomembrane and Membrane Protein, West China Hospital； Laboratory of Genetics, West China Second University Hospital, Sichuan University, Chengdu 610041, China； Department of Pathology, Chengdu Traditional Medicine University, Chengdu 610072, China； Division of Plant Protection, Yaan Agriculture Bureau, Yaan 625000, China； Department of Plant Pathology, Sichuan Agricultural University, Yaan 625000, China； Beijing Created Biotechnology Ltd., Beijing 100080, China； Division of Gastroenterology, University of Connecticut Health Center, Farmington 06030, USA

Abstract

Fungal pathogens represent major problems for human health and agriculture. As eukaryotic organisms, fungi share some important features with mammalian cells. Therefore, current anti-fungal antibiotics often can not distinguish between fungi and mammalian cells, resulting in serious side effects in mammalian cells. Accordingly, there is strong impetus to develop antifungal alternatives that are both safe and effective. The E1 family of colicin are channel-forming bacteriocins produced by Escherichia coli, which are bactericidal only to E. coli and related species. To target the channel-forming domain of colicin to fungal cell membrane, we engineered a sexual mating pheromone of Candida albicans, α-factor pheromone to colicin Ia. A peptide was constructed consisting of an α mating pheromone of C. albicans fused to the channel-forming domain of colicin Ia to create a new fusion protein, pheromonicin-CA (PMC-CA). Indirect immunolabeling showed that the PMC-CA bound to fungal cells and inhibited growth in the laboratory and field. In the field, the protective activity of pheromonicin against rice blast disease was significantly greater, on a molar basis, than that of triazoles, tricyclazole or isoprothiolane. These results suggest that fusion peptides may be of value as fungicidal agents under agricultural conditions.

Key words: bacteriocidal protein; mating pheromone; fusion fungicidal peptide

收稿日期：2012-09-14　　录用日期：2012-11-19

通讯作者：丘小庆　　E-mail: 491607484@qq.com

引用本文：

丘小庆, 仝崇毅, 钟真麒, 王万琪, 左越文, 黄云, 张璐, 张向利, 张红霞, 李荣旗, 王晶, 陈昊, 李芸芸, George Wu, 王和. 一种对抗植物病原真菌的工程化多结构域抗真菌多肽[J]. 生理学报 2013; 65 (4): 417-432.

QIU Xiao-Qing, TONG Chong-Yi, ZHONG Zhen-Qi, WANG Wan-Qi, ZUO Yue-Wen, HUANG Yun, ZHANG Lu, ZHANG Xiang-Li, ZHANG Hong-Xia, LI Rong-Qi, WANG Jing, CHEN Hao, LI Yun-Yun, WU George, WANG He. An engineered multidomain fungicidal peptide against plant fungal pathogens. Acta Physiol Sin 2013; 65 (4): 417-432 (in Chinese with English abstract).