Accumulation of antitumor polyketides by fermentation of Rubus delavayi Franch. with Clonostachys rogersoniana.

The aim of this work is to explore the effects of herbal medicine on secondary metabolites of microorganisms during fermentation. Clonostachys rogersoniana was found to metabolize only small amounts of polyketide glycosides rogerson B and C on fresh potatoes, but after replacing the medium to the medicinal plant Rubus delavayi Franch., the type and content of the metabolized polyketones showed significant changes. The sugars and glycosides in R. delavayi are probably responsible for the changes in secondary metabolites. Six polyketide glycosides including a new metabolite, rogerson F, and two potential antitumor compounds, TMC-151C and TMC-151D, were isolated from the extract of R. delavayi fermented by C. rogersoniana. In addition, 13C labeling experiments were used to trace the biosynthesis process of these compounds. TMC-151C and TMC-151D showed significant cytotoxic activity against PANC-1, K562 and HCT116 cancer cells but had no obvious cytotoxic activity against BEAS-2B human normal lung epithelial cells. The yields of TMC-151C and TMC-151D reached 14.37 ± 1.52 g/kg and 1.98 ± 0.43 g/kg, respectively, after fermentation at 28 °C for 30 days. This is the first study to confirm that herbal medicine can induce microbes to metabolize active compounds. And the technology of fermenting medicinal materials can bring more economic value to medicinal plants.

Biotransformation of α-terpineol by Alternaria alternata.

α-Terpineol (1), the main volatile constituent in some traditional Chinese medicines, has been reported to be metabolized to 4R-oleuropeic acid by the larvae of common cutworms. The present study verified that α-terpineol could be converted to 4R-oleuropeic acid (2) and (1S,2R,4R)-p-menthane-1,2,8-triol (3) by Alternaria alternata fermentation. Using shortened fermentation times, 7-hydroxy-α-terpineol (2a) was identified as an oxidative intermediate, which was consistent with the hypothesis put forward by previous studies. Cytochrome P450 enzymes were also confirmed to catalyze this biotransformation. This is the first study on the biotransformation of α-terpineol by microbial fermentation.

A new menthane-type monoterpenoid from fermented Illigera aromatica with Clonostachys rogersoniana 828H2.

A new menthane-type monoterpenoid, illigerate E (1), as well as two known ones, (1R*,3R*,4S*,6R*)-6,8-dihydroxymenthol (2) and cis-4-hydroxy-5-(1-hydroxy-1-methylethyl)-2-methyl-2-cyclohexene-1-one (3), were isolated from fermented Illigera aromatica with Clonostachys rogersoniana 828H2. Their structures were identified by HRESIMS and 1D/2D NMR spectra. Their inhibitory effects of NO production in RAW 264.7 macrophages were estimated.

Peniroquesines A-C: Sesterterpenoids Possessing a 5-6-5-6-5-Fused Pentacyclic Ring System from Penicillium roqueforti YJ-14.

Three novel sesterterpenes, peniroquesines A-C, possessing an 5-6-5-6-5-fused pentacyclic ring system, were isolated from the fungus Penicillium roqueforti YJ-14 by solid fermentation. Their structures were initially investigated in detail by NMR spectra and HR-ESI-MS and were further confirmed by chemical reaction experiments as well as by X-ray analysis. Furthermore, a plausible biosynthetic pathway was investigated by isotope-labeling experiments.