Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase
文献类型：期刊论文
| 作者 | Meng, Ling-Hong2,4 ; Awakawa, Takayoshi3,4; Li, Xiao-Ming2; Quan, Zhiyang3; Yang, Sui-Qun2; Wang, Bin-Gui2; Abe, Ikuro1,4
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| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
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| 出版日期 | 2024-05-21 |
| 页码 | 9 |
| 关键词 | Fungal natural products Indole alkaloid biosynthesis Heterologous expression Cytochrome P450 oxidase |
| ISSN号 | 1433-7851 |
| DOI | 10.1002/anie.202403963 |
| 通讯作者 | Awakawa, Takayoshi(takayoshi.awakawa@riken.jp) ; Wang, Bin-Gui(wangbg@ms.qdio.ac.cn) ; Abe, Ikuro(abei@mol.f.u-tokyo.ac.jp) |
| 英文摘要 | (+/-)-Penindolenes A-D (1-4), the first representatives of indole terpenoids featuring a gamma-lactam skeleton, were isolated from the mangrove-derived endophytic fungus Penicillium brocae MA-231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to gamma-lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae catalyzed the 2,3-cleavage of the indole ring to generate two keto groups in 1. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase-like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids. Novel enantiomeric natural indole terpenoids featuring a gamma-lactam skeleton were isolated from a mangrove-derived endophytic fungus. The cytochrome P450 enzyme was identified to catalyze the C2-C3 double bond cleavage of indole ring to generate products with two keto groups during the biosynthesis of gamma-lactam indole terpenoids. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. image |
| WOS关键词 | CYTOCHROME-P450 ENZYMES ; BIOLOGICAL-ACTIVITIES ; MECHANISM ; TRYPTOPHAN ; ALKALOIDS ; OXIDATION ; FUNGAL ; 2,3-DIOXYGENASE ; BIOSYNTHESIS ; CAMPTOTHECIN |
| 资助项目 | Japan Society for the Promotion of Science[JP20H00490] ; Japan Society for the Promotion of Science[JP20KK0173] ; Japan Society for the Promotion of Science[JP21H02636] ; Japan Society for the Promotion of Science[JP21K18246] ; Japan Society for the Promotion of Science[JP22H05123] ; New Energy and Industrial Technology Development Organization (NEDO)[JPNP20011] ; AMED[JP21ak0101164] ; National Natural Science Foundation of China[42176115] ; National Natural Science Foundation of China[U2006203] ; National Natural Science Foundation of China[41976090] ; Nagase Science Technology Foundation ; Mitsubishi Foundation ; Naito Foundation ; Yamada Science Foundation ; Chugai Foundation for Innovative Drug Discovery Science ; Chinese Academy of Sciences |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001227882700001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/185895]  |
| 专题 | 海洋研究所_实验海洋生物学重点实验室 |
| 通讯作者 | Awakawa, Takayoshi; Wang, Bin-Gui; Abe, Ikuro |
| 作者单位 | 1.Univ Tokyo, Collaborat Res Inst Innovat Microbiol, 1-1-1 Yayoi,Bunkyo Ku, Tokyo 1138657, Japan 2.Chinese Acad Sci, Inst Oceanol, CAS & Shandong Prov Key Lab Expt Marine Biol, Lab Marine Biol & Biotechnol, Nanhai Rd 7, Qingdao 266071, Peoples R China 3.RIKEN Ctr Sustainable Resource Sci, 2-1 Hirosawa, Wako, Saitama 3510198, Japan 4.Univ Tokyo, Grad Sch Pharmaceut Sci, 7-3-1 Hongo, Bunkyo Ku, Tokyo 1130033, Japan |
| 推荐引用方式 GB/T 7714 | Meng, Ling-Hong,Awakawa, Takayoshi,Li, Xiao-Ming,et al. Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2024:9. |
| APA | Meng, Ling-Hong.,Awakawa, Takayoshi.,Li, Xiao-Ming.,Quan, Zhiyang.,Yang, Sui-Qun.,...&Abe, Ikuro.(2024).Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,9. |
| MLA | Meng, Ling-Hong,et al."Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2024):9. |
入库方式： OAI收割
来源：海洋研究所
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