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A versatile terpene synthase (LcTPS2) producing unconventional macrocyclic terpenoids was characterized from Leucosceptrum canum. Engineered Escherichia coli and Nicotiana benthamiana expressing LcTPS2 produced six 18‐/14‐membered sesterterpenoids including five new ones and two 14‐membered diterpenoids. These products represent the first macrocyclic sesterterpenoids from plants and the largest sesterterpenoid ring system identified to date. Two variants F516A and F516G producing approximately 3.3‐ and 2.5‐fold, respectively, more sesterterpenoids than the wild‐type enzyme were engineered. Both 18‐ and 14‐membered ring sesterterpenoids displayed significant inhibitory activity on the IL‐2 and IFN‐γ production of T cells probably via inhibition of the MAPK pathway. The findings will contribute to the development of efficient biocatalysts to create bioactive macrocyclic sesterterpenoids, and also herald a new potential in the well‐trodden territory of plant terpenoid biosynthesis. [ABSTRACT FROM AUTHOR]

Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma‐bearing mice. It could reduce the number of myeloid‐derived suppressor cells (MDSC), as well as the expression of MDSC‐related molecule Arg‐1 and cytokines IL‐10 and TGF‐β, so that CD8+ T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL‐6 and IL‐1β were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor‐bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma‐bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Six new meroterpenoids, bipolarinoids A—F (1—6), and two known congeners (7—8) were isolated from a soil‐derived fungus Bipolaris zeicola. Their structures were elucidated based on extensive spectroscopic techniques (including HRESIMS and 1D and 2D NMR data), and the absolute configurations of 1—4 were further confirmed via single‐crystal X‐ray diffraction analysis and comparison of experimental electronic circular dichroism (ECD) data. Structurally, compound 1 represents the first case of cochlioquinone derivatives featuring a formaldehyde group at C‐11, and compound 3 features a rare amino group at C‐11. In the immunosuppressive activity assay, compounds 5—8 showed potent inhibitory activity against concanavalin A (ConA)‐induced T lymphocyte proliferation with IC50 values of 78.3, 81.1, 48.3, and 48.0 nmol/L, respectively, which provided promising leads for designing and developing new immunosuppressive agents to treat auto‐immunological diseases. [ABSTRACT FROM AUTHOR]

In this work, we report the preparation and evaluation of the in vitro and in vivo of the immunosuppressive activity of a series of lipophilic amino alcohols and diamines. All compounds were evaluated for inhibition of cell proliferation, cytotoxicity and NO production. Compounds 9, 12, 13, 17, and 18 did not display inhibition of cell proliferation while decreased NO production. The two most potent compounds, 13 and 17, submitted to delayed-type hypersensivity assays showed immunosuppressive activity. [ABSTRACT FROM AUTHOR]