Volatile compounds from the mycelium of the mushroom Agaricus bisporus

The pattern of volatiles from the mycelium of two commercial strains of Agaricus bisporus, grown in axenic culture on a semi-synthetic medium, was found to be broadly similar to that of the volatiles identified from sporophores. Tetrachloro-1,4-dimethoxybenzene, a known secondary metabolite of several Basidiomycetes, was found in the mycelium though not in the sporophores. [³⁶Cl]Tetrachloro-1,4-dimethoxybenzene was obtained when sodium [¹³Cl]chloride was added to the medium.     

Production of bioactive metabolites by submerged fermentation of the medicinal mushroom Antrodia cinnamomea: recent advances and future development

Edible and medicinal mushrooms have usually been considered as a sustainable source of unique bioactive metabolites, which are valued as promising provisions for human health. Antrodia cinnamomea is a unique edible and medicinal fungus widespread in Taiwan, which has attracted much attention in recent years for its high value in both scientific research and commercial applications owing to its potent therapeutic effects, especially for its hepatic protection and anticancer activity. Due to the scarcity of the fruiting bodies, the cultivation of A. cinnamomea by submerged fermentation appears to be a promising substitute which possesses some unique advantages, such as short culture time period and its high feasibility for scale-up production. However, the amount of fungal bioactive metabolites derived from the cultured mycelia of A. cinnamomea grown by submerged fermentation is much less than those obtained from the wild fruiting bodies. Hence, there is an urgent need to bridge such a discrepancy on bioactive metabolites between the wild fruiting bodies and the cultured mycelia. The objective of this article is to review recent advances and the future development of the mycelial submerged fermentation of A. cinnamomea in terms of enhancement for the production of fungal bioactive components by the optimization of culture conditions and the regulation of fungal metabolism. This review provides valuable information for further biotechnological applications of A. cinnamomea as well as other mushrooms being the source of bioactive ingredients by submerged fermentation.     

Selective peptide inhibitors of bifunctional thymidylate synthase‐dihydrofolate reductase from Toxoplasma gondii provide insights into domain–domain communication and allosteric regulation

The bifunctional enzyme thymidylate synthase–dihydrofolate reductase (TS–DHFR) plays an essential role in DNA synthesis and is unique to several species of pathogenic protozoans, including the parasite Toxoplasma gondii. Infection by T. gondii causes the prevalent disease toxoplasmosis, for which TS–DHFR is a major therapeutic target. Here, we design peptides that target the dimer interface between the TS domains of bifunctional T. gondii TS–DHFR by mimicking β‐strands at the interface, revealing a previously unknown allosteric target. The current study shows that these β‐strand mimetic peptides bind to the apo‐enzyme in a species‐selective manner to inhibit both the TS and distal DHFR. Fluorescence spectroscopy was used to monitor conformational switching of the TS domain and demonstrate that these peptides induce a conformational change in the enzyme. Using structure‐guided mutagenesis, nonconserved residues in the linker between TS and DHFR were identified that play a key role in domain–domain communication and in peptide inhibition of the DHFR domain. These studies validate allosteric inhibition of apo‐TS, specifically at the TS–TS interface, as a potential target for novel, species‐specific therapeutics for treating T. gondii parasitic infections and overcoming drug resistance.