Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase

doi:10.1002/anie.202403963

IOCAS-IR > 实验海洋生物学重点实验室

	Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase
	Meng, Ling-Hong1,2 ; Awakawa, Takayoshi 2,4; Li, Xiao-Ming 1; Quan, Zhiyang 4; Yang, Sui-Qun 1; Wang, Bin-Gui1 ; Abe, Ikuro 2,3
	2024-05-21
发表期刊	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
ISSN	1433-7851
页码	9
通讯作者	Awakawa, Takayoshi([email protected]) ; Wang, Bin-Gui([email protected]) ; Abe, Ikuro([email protected])
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
关键词	Fungal natural products Indole alkaloid biosynthesis Heterologous expression Cytochrome P450 oxidase
DOI	10.1002/anie.202403963
收录类别	SCI
语种	英语
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
WOS类目	Chemistry, Multidisciplinary
WOS记录号	WOS:001227882700001
出版者	WILEY-V C H VERLAG GMBH
WOS关键词	CYTOCHROME-P450 ENZYMES ; BIOLOGICAL-ACTIVITIES ; MECHANISM ; TRYPTOPHAN ; ALKALOIDS ; OXIDATION ; FUNGAL ; 2,3-DIOXYGENASE ; BIOSYNTHESIS ; CAMPTOTHECIN
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/185896
专题	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.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 2.Univ Tokyo, Grad Sch Pharmaceut Sci, 7-3-1 Hongo, Bunkyo Ku, Tokyo 1130033, Japan 3.Univ Tokyo, Collaborat Res Inst Innovat Microbiol, 1-1-1 Yayoi,Bunkyo Ku, Tokyo 1138657, Japan 4.RIKEN Ctr Sustainable Resource Sci, 2-1 Hirosawa, Wako, Saitama 3510198, Japan
第一作者单位	中国科学院海洋研究所
通讯作者单位	中国科学院海洋研究所
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.