Refactoring the Concise Biosynthetic Pathway of Cyanogramide Unveils Spirooxindole Formation Catalyzed by a P450 Enzyme
文献类型：期刊论文
| 作者 | Zhu, Yiguang2; Zhang, Qingbo2; Fang, Chunyan; Zhang, Yingli1; Ma, Liang2; Liu, Zhiwen; Zhai, Shilan; Peng, Jing; Zhang, Liping2; Zhu, Weiming3 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2020 |
| 卷号 | 59期号:33页码:14065 |
| 关键词 | alkaloids biosynthesis cyanogramide heterologous expression spirooxindoles |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202004978 |
| 英文摘要 | Cyanogramide (1) from the marine actinomycete Actinoalloteichus cyanogriseus WH1-2216-6 features a unique spirooxindole skeleton and exhibits significant bioactivity to efficiently reverse drug resistance in tumor cells. The biosynthetic gene cluster of 1 in A. cyanogriseus WH1-2216-6 was identified and refactored by promoter engineering for heterologous expression in Streptomyces coelicolor YF11, thereby enabling the production of 1 and five new derivatives. Interesting, four of them, including 1, were identified as enantiomeric mixtures in different ratios. The functions of tailoring enzymes, including two methyltransferases (CyaEF), and three cytochrome P450 monooxygenases (CyaGHI) were confirmed by gene inactivation and feeding experiments, leading to the elucidation of a concise biosynthetic pathway for 1. Notably, CyaH was biochemically verified to catalyze the formation of the spirooxindole skeleton in 1 through an unusual carbocation-mediated semipinacol-type rearrangement reaction. |
| 资助机构 | Qingdao National Laboratory for Marine Science and Technology [QNLM2016ORP0304]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31670046, 31630004]; Chinese Academy of SciencesChinese Academy of Sciences [QYZDJ-SSW-DQC004]; Guangdong Province [GDME-2018C005]; Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [GML2019ZD0406]; National Key Research and Development Program of China [2018YFA0901903]; Special Support Program for Training High-Level Talents in Guangdong [2019TQ05H299] ; Qingdao National Laboratory for Marine Science and Technology [QNLM2016ORP0304]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31670046, 31630004]; Chinese Academy of SciencesChinese Academy of Sciences [QYZDJ-SSW-DQC004]; Guangdong Province [GDME-2018C005]; Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) [GML2019ZD0406]; National Key Research and Development Program of China [2018YFA0901903]; Special Support Program for Training High-Level Talents in Guangdong [2019TQ05H299] |
| 源URL | [http://ir.scsio.ac.cn/handle/344004/18401]  |
| 专题 | 南海海洋研究所_中科院海洋生物资源可持续利用重点实验室 |
| 作者单位 | 1.Southern Marine Sci & Engn Guangdong Lab Guangzho, 1119 Haibin Rd, Guangzhou 511458, Peoples R China 2.Chinese Acad Sci, Guangdong Key Lab Marine Mat Med, Innovat Acad South China Sea Ecol & Environm Engn, South China Sea Inst Oceanol,Key Lab Trop Marine, 164 West Xingang Rd, Guangzhou 510301, Peoples R China 3.Hebei Normal Univ, Coll Life Sci, Shijiazhuang 050024, Hebei, Peoples R China 4.Ocean Univ China, Sch Med & Pharm, Chinese Minist Educ, Key Lab Marine Drugs, Qingdao 266003, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Yiguang,Zhang, Qingbo,Fang, Chunyan,et al. Refactoring the Concise Biosynthetic Pathway of Cyanogramide Unveils Spirooxindole Formation Catalyzed by a P450 Enzyme[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2020,59(33):14065, 14069. |
| APA | Zhu, Yiguang.,Zhang, Qingbo.,Fang, Chunyan.,Zhang, Yingli.,Ma, Liang.,...&Zhang, Changsheng.(2020).Refactoring the Concise Biosynthetic Pathway of Cyanogramide Unveils Spirooxindole Formation Catalyzed by a P450 Enzyme.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,59(33),14065. |
| MLA | Zhu, Yiguang,et al."Refactoring the Concise Biosynthetic Pathway of Cyanogramide Unveils Spirooxindole Formation Catalyzed by a P450 Enzyme".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 59.33(2020):14065. |
入库方式： OAI收割
来源：南海海洋研究所
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