Insights into Bacterial 6-Methylsalicylic Acid Synthase and Its Engineering to Orsellinic Acid Synthase for Spirotetronate Generation
文献类型：期刊论文
| 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) |
| 刊名 | Chem. Biol.
 |
| 出版日期 | 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 |
| 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. |
入库方式： OAI收割
来源：上海有机化学研究所
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