GSNOR regulates ganoderic acid content in Ganoderma lucidum under heat stress through S-nitrosylation of catalase

As a master regulator of the balance between NO signaling and protein S-nitrosylation, S-nitrosoglutathione (GSNO) reductase (GSNOR) is involved in various developmental processes and stress responses. However, the proteins and specific sites that can be S-nitrosylated, especially in microorganisms, and the physiological functions of S-nitrosylated proteins remain unclear. Herein, we show that the ganoderic acid (GA) content in GSNOR-silenced (GSNORi) strains is significantly lower (by 25%) than in wild type (WT) under heat stress (HS). Additionally, silencing GSNOR results in an 80% increase in catalase (CAT) activity, which consequently decreases GA accumulation via inhibition of ROS signaling. The mechanism of GSNOR-mediated control of CAT activity may be via protein S-nitrosylation. In support of this possibility, we show that CAT is S-nitrosylated (as shown via recombinant protein in vitro and via GSNORi strains in vivo). Additionally, Cys (cysteine) 401, Cys642 and Cys653 in CAT are S-nitrosylation sites (assayed via mass spectrometry analysis), and Cys401 may play a pivotal role in CAT activity. These findings indicate a mechanism by which GSNOR responds to stress and regulates secondary metabolite content through protein S-nitrosylation. Our results also define a new S-nitrosylation site and the function of an S-nitrosylated protein regulated by GSNOR in microorganisms.

Improvement of cytotoxicity and necrosis activity of ganoderic acid a through the development of PMBN-A.Her2-GA as a targeted nano system

In this article, GA-A is used for the first time as a natural agent for targeting breast cancer cells based on the newly developed nano carrier as a targeted DDS.

Mushrooms (Basidiomycetes) as a significant source of biologically active compounds for malaria control

Mushrooms represent a large family of fleshy fungi that have been of high interest since ancient ages due to their medicinal and nutritional importance. Therefore, it can represent a significant source of bioactive compounds in malaria control. The few numbers of studies on <i>in vitro</i> antiplasmodial and insecticidal properties of their extracts and chemical constituents led to interesting results reported in numerous scientific publications. This review aims to provide a comprehensive compilation of literature up to 2021 on the antiplasmodial, insecticidal as well as cytotoxic chemical constituents of medicinal mushrooms that can help in the management of malaria both against the parasite <i>Plasmodium falciparum</i> and the mosquitoe <i>Anopheles stephensis</i> acting as a vector of malaria through its bites. For this purpose, some searches have been done in some online libraries using keywords like Basidiomycete, mushroom, malaria, <i>Plasmodium</i>, <i>Anopheles</i> and antiplasmodial without language restriction. Among the reported compounds, 51 selected ones displayed significant antiplasmodial potency with IC₅₀ values lower than 10 μM against <i>P. falciparum</i> strains sensitive or resistant to chloroquine. For instance, ganoderic acid AW1 demonstrated a strong antiplasmodial activity with IC₅₀ of 257.8 nM against <i>P. falciparum</i> D6, while strong activities were displayed by ganoweberianones A (IC₅₀ = 0.050 μM) and B (IC₅₀ = 0.46 μM) against <i>P. falciparum</i> K1. Moreover, some mushroom methanol extracts demonstrated good larvicidal and ovicidal activities against <i>Anopheles stephensis</i>. This paper provides further insights into the development of new antiplasmodial drugs or new potent eco-friendly pesticides to control mosquito vectors.

Glycosylation of Ganoderic Acid G by Bacillus Glycosyltransferases

Ganoderma lucidum is a medicinal fungus abundant in triterpenoids, its primary bioactive components. Although numerous Ganoderma triterpenoids have already been identified, rare Ganoderma triterpenoid saponins were recently discovered. To create novel Ganoderma saponins, ganoderic acid G (GAG) was selected for biotransformation using four Bacillus glycosyltransferases (GTs) including BtGT_16345 from the Bacillus thuringiensis GA A07 strain and three GTs (BsGT110, BsUGT398, and BsUGT489) from the Bacillus subtilis ATCC 6633 strain. The results showed that BsUGT489 catalyzed the glycosylation of GAG to GAG-3-o-β-glucoside, while BsGT110 catalyzed the glycosylation of GAG to GAG-26-o-β-glucoside, which showed 54-fold and 97-fold greater aqueous solubility than that of GAG, respectively. To our knowledge, these two GAG saponins are new compounds. The glycosylation specificity of the four Bacillus GTs highlights the possibility of novel Ganoderma triterpenoid saponin production in the future.