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学科主题: 生命有机化学
题名: 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
作者: 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)
通讯作者: 刘文
刊名: Chem. Biol.
发表日期: 2010
卷: 17, 期:5, 页:495-503
收录类别: SCI
部门归属: 中国科学院上海有机化学研究所; 兰州大学
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.
语种: 英语
相关网址: 查看原文
WOS记录号: WOS:000278845000011
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/28459
Appears in Collections:生命有机化学国家重点实验室_期刊论文

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Recommended Citation:
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.
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