Bioactive Sesquiterpenes from the Edible Mushroom Flammulina velutipes and Their Biosynthetic Pathway Confirmed by Genome Analysis and Chemical Evidence

Abstract

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 IC of 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 IC of 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.

Genetic diversity and structure of core collection of winter mushroom (Flammulina velutipes) developed by genomic SSR markers

“…Meanwhile, several economically important agronomic traits, such as tolerance to high temperature and rich contents of sesquiterpenes, can also be found in wild strains [30, 40]. In the cultivation of F. velutipes , temperature is usually an important limiting factor.…”

“…In fact, we did find a wild strain (F98), collected from Longling, Yunnan, that can grow more vigorously than cultivars at a higher temperature (18 °C) [30]. Further analyses on chemical components showed that this strain contains 15 new sesquiterpenes with various skeletons, some of which showed moderate antidiabetes and antitumor bioactivity [40]. Thus, it is quite essential to keep as many wild strains as possible in constructing a core collection for F. velutipes .…”

Genome-wide analysis and prediction of genes involved in the biosynthesis of polysaccharides and bioactive secondary metabolites in high-temperature-tolerant of wild Flammulina filiformis

“…It has been reported that China is currently the largest producer of F. filiformis, with an annual production of 2.4 million tons [3]. F. filiformis also possesses tremendous pharmaceutical values, and many bioactive constituents have been identified such as polysaccharides [4][5][6], flavonoids [7], sesquiterpenes, glycosides, proteins, and phenols [8][9][10]. These compounds have been shown to exhibit antitumour, anticancer, anti-atherosclerotic thrombosis inhibition, anti-aging and antioxidant effects [11,12].…”

“…Most interestingly, the chemical composition of the wild strain was different from that of other commercially cultivated strains of F. filiformis, harbouring more unique chemical compounds. A total of 13 new sesquiterpenes with noreudesmane, spiroaxane, cadinane, and cuparane skeletons were isolated and identified from the wild strain Liu355 [9].…”

Structural characterization of polysaccharides from Cordyceps militaris and their hypolipidemic effects in high fat diet fed mice

“…20,33,46,47 HMGR is a glycoprotein of the endoplasmic reticulum that participates in the mevalonate pathway, and it is a rate-limiting enzyme in cholesterol synthesis pathway. 48 Thus, targeting HMGR may serve as a promising therapeutic treatment for hyperlipidemia. In the present study, according to the results of ELISA experiments, we found the hepatic HMGR activity was remarkably lower in PC group (p < 0.05), compared with HC mice (Fig.…”