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Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation
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
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)
2010
发表期刊Chem. Biol.
ISSN1074-5521
卷号17期号:5页码:495-503
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.
学科领域生命有机化学
部门归属中国科学院上海有机化学研究所; 兰州大学
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收录类别SCI
语种英语
WOS记录号WOS:000278845000011
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被引频次:22[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/28459
专题生命有机化学国家重点实验室
通讯作者Liu W(刘文)
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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.
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