Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase

doi:10.1186/s12934-015-0337-y

CORC > 中国农业科学院 > 植物保护研究所

	Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase
	Zhang, Ji 1; Yan, Yi-Jun 1,3; An, Jing 1; Huang, Sheng-Xiong 3; Wang, Xiang-Jing 1; Xiang, Wen-Sheng 1,2
刊名	MICROBIAL CELL FACTORIES
	2015
卷号	14 页码:-
关键词	25-Ethyl ivermectin 25-Methyl ivermectin Domain swap Insecticidal activity
ISSN号	1475-2859
DOI	10.1186/s12934-015-0337-y
通讯作者	Zhang, Ji
英文摘要	Background: Avermectin and milbemycin are important 16-membered macrolides that have been widely used as pesticides in agriculture. However, the wide use of these pesticides inevitably causes serious drug resistance, it is therefore imperative to develop new avermectin and milbemycin analogs. The biosynthetic gene clusters of avermectin and milbemycin have been identified and the biosynthetic pathways have been elucidated. Combinatorial biosynthesis by domain swap provides an efficient strategy to generate chemical diversity according to the module polyketide synthase (PKS) assembly line.Results: The substitution of aveDH2-KR2 located in avermectin biosynthetic gene cluster in the industrial avermectin-producing strain Streptomyces avermitilis NA-108 with the DNA regions milDH2-ER2-KR2 located in milbemycin biosynthetic gene cluster in Streptomyces bingchenggensis led to S. avermitilis AVE-T27, which produced ivermectin B1a with high yield of 3450 +/- 65 mu g/ml. The subsequent replacement of aveLAT-ACP encoding the loading module of avermectin PKS with milLAT-ACP encoding the loading module of milbemycin PKS led to strain S. avermitilis AVE-H39, which produced two new avermectin derivatives 25-ethyl and 25-methyl ivermectin (1 and 2) with yields of 951 +/- 46 and 2093 +/- 61 mu g/ml, respectively. Compared to commercial insecticide ivermectin, the mixture of 25-methyl and 25-ethyl ivermectin (2:1 = 3:7) exhibited 4.6-fold increase in insecticidal activity against Caenorhabditis elegans. Moreover, the insecticidal activity of the mixture of 25-methyl and 25-ethyl ivermectin was 2.5-fold and 5.7-fold higher than that of milbemycin A3/A4 against C. elegans and the second-instar larva of Mythimna separate, respectively.Conclusions: Two new avermectin derivatives 25-methyl and 25-ethyl ivermectin were generated by the domain swap of avermectin PKS. The enhanced insecticidal activity of 25-methyl and 25-ethyl ivermectin implied the potential use as insecticide in agriculture. Furthermore, the high yield and genetic stability of the engineered strains S. avermitilis AVE-T27 and AVE-H39 suggested the enormous potential in industrial production of the commercial insecticide ivermectin and 25-methyl/25-ethyl ivermectins, respectively.
学科主题	Biotechnology & Applied Microbiology
语种	英语
出版者	BIOMED CENTRAL LTD
WOS记录号	WOS:000361650700001
内容类型	期刊论文
源URL	[http://111.203.20.206/handle/2HMLN22E/11637]
专题	植物保护研究所
作者单位	1.Northeast Agr Univ, Sch Life Sci, Harbin 150030, Peoples R China 2.Chinese Acad Agr Sci, Inst Plant Protect, State Key Lab Biol Plant Dis & Insect Pests, Beijing 100193, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, Kunming 650201, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Ji,Yan, Yi-Jun,An, Jing,et al. Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase[J]. MICROBIAL CELL FACTORIES,2015,14:-.
APA	Zhang, Ji,Yan, Yi-Jun,An, Jing,Huang, Sheng-Xiong,Wang, Xiang-Jing,&Xiang, Wen-Sheng.(2015).Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase.MICROBIAL CELL FACTORIES,14,-.
MLA	Zhang, Ji,et al."Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase".MICROBIAL CELL FACTORIES 14(2015):-.