Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation

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	Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation
	Ding W(丁伟) ; Lei C(雷春) ; He QL(贺庆利) ; Zhang Q(张琪) ; Bi YR(毕玉蓉) ; Liu W(刘文)
刊名	Chem. Biol.
	2010
卷号	17 期号:5 页码:495-503
ISSN号	1074-5521
其他题名	洞察细菌6-甲基水杨酸合成酶及其转化为苔色酸合成酶的代谢工程改造有利于螺环乙酰乙酸内酯产生
通讯作者	刘文
英文摘要	The enzymes 6-methylsalicylic acid (6-MSA) synthases (6-MSASs) are involved in the building of an aryl moiety in many bioactive secondary metabolites produced by fungi and bacteria. Using the bacterial 6-MSAS ChIB1 in the biosynthesis of spirotetronate antibiotic chlorothricin (CHL) as a model, functional analysis of its dehydratase (DH) and ketoreductase (KR) domains by site-specific mutagenesis revealed that selective ketoreduction is not essential for polyketide chain extension. Promiscuity of the ketoacylsynthase domain in beta functionality recognition allows for engineering ChIB1 to an orsellinic acid (OSA) synthase (OSAS) by inactivating KR at the active site. The engineered ChIB1 is compatible with the enzymes for late-stage tailoring in CHL biosynthesis, featuring specific protein recognitions that facilitate variable aryl group incorporation. The resulting spirotetronates, which bear an OSA-derived aryl group, exhibited antibacterial activities comparable to those of the parent products.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1016/j.chembiol.2010.04.009
语种	英语
WOS记录号	WOS:000278845000011
公开日期	2013-08-23
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/28459]
专题	上海有机化学研究所_生命有机化学国家重点实验室
推荐引用方式 GB/T 7714	Ding W,Lei C,He QL,et al. Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation[J]. Chem. Biol.,2010,17(5):495-503.
APA	丁伟,雷春,贺庆利,张琪,毕玉蓉,&刘文.(2010).Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation.Chem. Biol.,17(5),495-503.
MLA	丁伟,et al."Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation".Chem. Biol. 17.5(2010):495-503.