机构：[1]Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, 510632 Guangzhou, People’s Republic of China.[2]Clinical Experimental Center, First Affiliated Hospital of Jinan University, 510630 Guangzhou, People’s Republic of China.[3]Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 HongoBunkyo-kuTokyo 113-0033, Japan.
Furanosteroids, represented by wortmannin, viridin, and demethoxyviridin, are a special group of fungal-derived, highly oxygenated steroids featured by an extra furan ring. They are well-known nanomolar-potency inhibitors of phosphatidylinositol 3-kinase and widely used in biological studies. Despite their importance, the biosyntheses of these molecules are poorly understood. Here, we report the identification of the biosynthetic gene cluster for demethoxyviridin, consisting of 19 genes, and among them 15 biosynthetic genes, including six cytochrome P450 monooxygenase genes, are deleted. As a result, 14 biosynthetic intermediates are isolated, and the biosynthetic pathway for demethoxyviridin is elucidated. Notably, the pregnane side-chain cleavage requires three enzymes: flavin-dependent Baeyer-Villiger monooxygenase, esterase, and dehydrogenase, in sharp contrast to the single cytochrome P450-mediated process in mammalian cells. Structure-activity analyses of these obtained biosynthetic intermediates reveal that the 3-keto group, the C1β-OH, and the aromatic ring C are important for the inhibition of phosphatidylinositol 3-kinase.
基金：
This work was mainly supported by grants from the National Natural Science Foundation
of China (31670036, 3171101305, and 81673315), the 111 Project of Ministry of
Education of the People’s Republic of China (B13038), the JST/NSFC Strategic International Collaborative Research Program, Japanese-Chinese Collaborative Research
Program, Chang Jiang Scholars Program (Hao Gao, 2017) from the Ministry of Education
of China, Guangdong Special Support Program (2016TX03R280), Guangdong
Province Universities and Colleges Pearl River Scholar Funded Scheme (Hao Gao, 2014),
and K. C. Wong Education Foundation (Hao Gao, 2016), Guangzhou Science and
Technology Project (201707010266), Kobayashi International Scholarship Foundation, a
Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan (JSPS KAKENHI grant numbers JP15H01836 and
JP16H06443).
语种：
外文
PubmedID：
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最新[2025]版：
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第一作者：
第一作者机构：[1]Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, 510632 Guangzhou, People’s Republic of China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Gao-Qian Wang,Guo-Dong Chen,Sheng-Ying Qin,et al.Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage.[J].Nature communications.2018,9(1):1838.doi:10.1038/s41467-018-04298-2.
APA：
Gao-Qian Wang,Guo-Dong Chen,Sheng-Ying Qin,Dan Hu,Takayoshi Awakawa...&Hao Gao.(2018).Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage..Nature communications,9,(1)
MLA：
Gao-Qian Wang,et al."Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage.".Nature communications 9..1(2018):1838
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