Fungal Bergamotane Sesquiterpenoids—Potential Metabolites: Sources, Bioactivities, and Biosynthesis

Abstract

The marine environment represents the largest ecosystem on the Earth’s surface. Marine-derived fungi are of remarkable importance as they are a promising pool of diverse classes of bioactive metabolites. Bergamotane sesquiterpenoids are an uncommon class of terpenoids. They possess diverse biological properties, such as plant growth regulation, phototoxic, antimicrobial, anti-HIV, cytotoxic, pancreatic lipase inhibition, antidiabetic, anti-inflammatory, and immunosuppressive traits. The current work compiles the reported bergamotane sesquiterpenoids from fungal sources in the period ranging from 1958 to June 2022. A total of 97 compounds from various fungal species were included. Among these metabolites, 38 compounds were derived from fungi isolated from different marine sources. Furthermore, the biological activities, structural characterization, and biosynthesis of the compounds are also discussed. The summary in this work provides a detailed overview of the reported knowledge of fungal bergamotane sesquiterpenoids. Moreover, this in-depth and complete review could provide new insights for developing and discovering new valuable pharmaceutical agents from these natural metabolites.

An indole diketopiperazine alkaloid and a bisabolane sesquiterpenoid with unprecedented skeletons from Aspergillus fumigatus

“…17 Due to their fascinating structures and biological activities, indole diketopiperazines and sesquiterpenoids have attracted increasing attention from the biosynthetic, organic synthetic, and phytochemical communities. 6,7,[21][22][23] The fungus Aspergillus fumigatus is a rich source of indole diketopiperazines, notably neoechinulin A (R1), which exhibited a potent inhibitory effect against SARS-CoV-2 M pro with an IC 50 value of 0.47 μM, which is comparable to the reference standard GC376. 24 In addition to indole diketopiperazine, spirolactam alkaloids [pseurotin A (R6) had inhibitory effect on glioma cells with an IC 50 value of 0.51 μM], fumiquinazolines [fumiquinazoline A (R7) possessed antifeedant activity with antifeedant index of 45.0%], tryptoquivalines [tryptoquivaline J (R8) inhibited the proliferation of breast cancer cells], terpenoids [ pyripyropene A (R11) displayed inhibition of cholesterol acyltransferase with an IC 50 value of 0.058 μM], and polyketones [sulfurasperine D (R14) exhibited antioxidant activity with an IC 50 value of 1.65 μM] are also their metabolites, as shown in Fig.…”

“…17 Due to their fascinating structures and biological activities, indole diketopiperazines and sesquiterpenoids have attracted increasing attention from the biosynthetic, organic synthetic, and phytochemical communities. 6,7,21–23…”