A Novel Derivative of (-)mycousnine Produced by the Endophytic Fungus Mycosphaerella nawae, Exhibits High and Selective Immunosuppressive Activity on T Cells

Abstract

An endophytic fungus, Mycosphaerella nawae ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages. Furthermore, the cytotoxicity of (-)mycousnine enamine was lower than that of cyclosporin A, and its therapeutic index (TC50/EC50) was 4,463.5, which is five-fold higher than that of cyclosporin A. We conclude that (-)mycousnine enamine (2), the semi-synthestic product prepared from the native product (-)mycousnine (1) of the endophyte M. nawae is a novel effective immunosuppressant showing low toxicity and high selectivity.

Gut fungal dysbiosis and altered bacterial‐fungal interaction in patients with diarrhea‐predominant irritable bowel syndrome: An explorative study

“…We identified specific fungal genera including Mycosphaerella , Aspergillus , Sporidiobolus, and Pandora which may potentially discriminate D‐IBS from HC Mycosphaerella could produce and release mycousnine, a selective and low‐toxic immunosuppressant, which involves in immune regulation and host defense 40 . The decrease of Mycosphaerella in D‐IBS patients was likely to induce intestinal immune activation and participate in the pathogenesis of D‐IBS 41 .…”

Plant associated fungal endophytes as a source of natural bioactive compounds

“…However, its amide derivative mycousnine enamine is shown to possess the immunosuppressive activity through inhibition of T-cell proliferation but not B-cell proliferation. The amide derivative suppresses the T-cell surface antigen such as the cluster of differentiation (CD69 and CD25) and cytokine such as interleukin-2 and interferon-γ (Wang et al 2017 ). The fungal endophyte BAK-I isolated from the bark of plant Kigelia Africana (Lam.)…”

Pharmacological Potential of Fungal Endophytes Associated with Medicinal Plants: A Review

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