Bioactive Sesquiterpenes from the Edible Mushroom Flammulina velutipes and Their Biosynthetic Pathway Confirmed by Genome Analysis and Chemical Evidence.
Twelve putative sesquiterpene synthases genes were found in clades along with enzymes with 1,6-, 1,10-, and 1,11-cyclase activities in the genome of Flammulina velutipes. Chemistry investigation of F. velutipes led to the identification of two seco-cuparane sesquiterpenes, flammufuranone A (1) and B (2); 13 new sesquiterpenes with nor-eudesmane, spiroaxane, cadinane, and cuparane skeletons (3-14, 16); as well as two new ergosterol derivatives (17 and 18). Sesquiterpenes (3-14) derived from 1,10-cyclizing enzyme were first reported from this mushroom. The absolute configurations in 1 (3R,7S) and 2 (3R,7R) were assigned by electronic circular dichroism (ECD) calculation. The absolute configuration in 3 was confirmed by X-ray diffraction analysis. The absolute configurations in the 1,2-diol moiety of 13, and in the 1,3-diol moiety of 17 and 18 were determined using Snatzke's method. Among these compounds, 3, 5, 13, and 14 were found to inhibit the HMG-CoA reductase with IC50of 114.7, 77.6, 55.5, and 87.1 μM, respectively. Compounds 5, 6, 7, 10, 13, and 14 showed DPP-4 inhibitory activity with IC50of 75.9, 83.7, 70.9, 79.7, 80.5, and 74.8 μM, respectively. The biosynthesis for sesquiterpenes in F. velutipes was also discussed.
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.|Savaid Medical School, University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Qiaoqiao
Q
Tao
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.
Ke
K
Ma
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.
Yanlong
Y
Yang
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.|Savaid Medical School, University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Kai
K
Wang
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.|Savaid Medical School, University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Baosong
B
Chen
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.
Ying
Y
Huang
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.
Junjie
J
Han
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.
Li
L
Bao
Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China.
Xiao-Bin
XB
Liu
Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China.
Zhuliang
Z
Yang
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.|Savaid Medical School, University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Wen-Bing
WB
Yin
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.|Savaid Medical School, University of Chinese Academy of Sciences , Beijing 100049, People's Republic of China.
Hongwei
H
Liu
D000363:Agaricales / Q000737:chemistry* / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D016681:Genome, Fungal; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000378:metabolism; D013057:Spectrum Analysis / Q000379:methods
D012717:Sesquiterpenes