Epigenetic Manipulation to Trigger Production of Guaiane-Type Sesquiterpenes from a Marine-Derived Spiromastix sp. Fungus with Antineuroinflammatory Effects

Abstract

Epigenetic manipulation of a deep-sea sediment-derived Spiromastix sp. fungus using suberoylanilide hydroxamic acid (SAHA) induction resulted in the activation of a terpene-related biosynthetic gene cluster, and nine new guaiane-type sesquiterpenes, spiromaterpenes A-I (1–9), were isolated. Their structures were determined using various spectroscopic techniques, in association with the modified Mosher’s method, computed electronic circular dichroism (ECD) spectra, and chemical conversion for configurational assignments. Compounds 4–6 exhibited significant effects against the NO production on lipopolysaccharide (LPS)-induced microglia cells BV2, and the preliminary SAR analyses demonstrated that a 2­(R),11-diol unit is favorable. The most active 5 abolished LPS-induced NF-κB translocation from the cytosol to the nucleus in BV-2 microglial cells, accompanied by the marked reduction of the transcription levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α dose-dependently in both LPS-induced BV-2 and BV-2 cells, as well as the protein and mRNA levels of iNOS and COX-2. This study complements the gap in knowledge regarding the anti-neuroinflammatory activity of guaiane-type sesquiterpenoids at the cellular level and suggests that 5 is promising for further optimization as a multifunctional agent for antineuroinflammation.

γ‐Aromatic Butenolides of Microbial Source – A Review of Their Structures, Biological Activities and Biosynthesis

“…3-hydroxy-4-(4-hydroxyphenyl)-5-methoxycarbonyl-5-(4-hydroxy-3-formylben-zyl)-2,5-dihydro-2-furanone (9) was isolated from the gorgonian corals Echinogorgia aurantiaca endophytic fungus A. terreus. Two new butyrolactone derivatives, isobutyrolactone II (12) and 4-O-demethylisobutyrolactone II (18) were isolated from the soil-dwelling fungus A. terreus by Chen's team. An endophytic fungal strain Aspergillus versicolor derived from the rhizome of Paris polyphylla var.…”

“…With a continuous increase in the number of new compounds, there have been several review articles on γ ‐AB [13–18] . For example, Joe and his co‐workers have reviewed the butenolactones in marine microbes, yet they focused only on three types of butenolides (rubrolides, cadiolides and prunolides), from marine tunicates [19] .…”

“…With a continuous increase in the number of new compounds, there have been several review articles on γ-AB. [13][14][15][16][17][18] For example, Joe and his co-workers have reviewed the butenolactones in marine microbes, yet they focused only on three types of butenolides (rubrolides, cadiolides and prunolides), from marine tunicates. [19] Studies on synthetic strategies and related NPs for γ-butenolides from 2010 to 2020 were reviewed by Chatterjee et al, focusing on the synthesis of γ-butenolide and γ-alkylidenebutenolides, but they did not cover much about the isolation, structural diversities.…”

Two New Sulfate-Modified Dibenzopyrones With Anti-foodborne Bacteria Activity From Sponge-Derived Fungus Alternaria sp. SCSIOS02F49

“…In recent years, marine fungi have received widespread attention because of their tremendous capacity to produce structurally unique compounds with a broad range of pharmacological properties (Radic and Strukelj, 2012 ; Pang et al, 2016 ; Fang et al, 2021 ; Guo et al, 2021 ). Over the last 5 years, discoveries of new compounds from marine fungi have outpaced discoveries from all other marine phyla.…”

Pro-angiogenic New Chloro-Azaphilone Derivatives From the Hadal Trench-Derived Fungus Chaetomium globosum YP-106

“…In the past 50 years, about 20,000 natural products have been reported from marine microorganisms, but the number of natural products reported from deep-sea microorganisms is very low, less than 2%, and hadal trench (>6,000 m) microorganisms are hardly reported (Skropeta and Wei, 2014;Carroll et al, 2021). In recent years, with the rapid development of sample collection, identification, and culture techniques of microorganisms, the chemical study of deep-sea fungi has shown a dramatic increase, and researchers have found a wealth of novel active secondary metabolites with pro-angiogenic (Fan et al, 2015;Yan et al, 2022), antibacterial (Wang et al, 2016;Chi et al, 2020b), anti-inflammatory (Guo et al, 2021), anticancer (Chi et al, 2020a), and other biological activities (Wang et al, 2020) from deep-sea microorganisms.…”