Suberoylanilide Hydroxamic Acid, a Histone Deacetylase Inhibitor, Induces the Production of Anti-inflammatory Cyclodepsipeptides from Beauveria felina

Abstract

The addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid to a culture of the filamentous fungus Beauveria felina significantly changed its secondary metabolite profile and led to the isolation of eight compounds, including three new cyclodepsipeptides, desmethylisaridin E (1), desmethylisaridin C2 (2), and isaridin F (3), along with five known cyclodepsipeptide compounds. Isaridin F (3) possesses a cyclodepsipeptide ring with N-methylbutyric acid, which is rare in natural peptides. Absolute configurations of the new cyclodepsipeptides were achieved by Marfey's method. The anti-inflammatory activity of the isolated compounds was investigated through evaluating their effect on superoxide anion production and elastase release by FMLP-induced human neutrophils. Among the tested compounds, desmethylisaridin E (1) inhibited superoxide anion production and desmethylisaridin C2 (2) inhibited elastase release, with IC50 values of 10.00 ± 0.80 and 10.01 ± 0.46 μM, respectively.

Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from Hapsidospora irregularis

“…5 Calcium is a versatile and critical second messenger in all cells. Stimulation and inhibition of changes in intracellular calcium content caused by 1–7 was assessed in lobar bronchial epithelial cells.…”

“…As shown in Figure 3B, a 4,534-bp fragment was amplified from the correct double crossover mutant with primers A and B, and a 5,026-bp fragment with primers C and D. Because primers B and C were specifically from the hygromycin resistance gene ( HygR ) in the vector, no PCR products were obtained from the wild type. This correct mutant was then grown on the oatmeal agar modified from WSH agar 5 for product analysis. As shown in Figure 3C, when grown in the oatmeal medium, the wild type produces 1 and 2 as the major metabolites (traces i-iii).…”

One strain-many compounds (OSMAC) method for production of polyketides, azaphilones, and an isochromanone using the endophytic fungus Dothideomycete sp.

“…The present study suggests that endophytic fungi are potentially suitable microorganisms for the OSMAC method, which could enhance the chemical diversity of secondary metabolites. Recently, endophytic fungi are used as metabolite producers through the OSMAC method, for example, by varying culture media for the fungus Aspergillus fumigatus (Zhang et al, 2013) and by addition of histone deacetylase inhibitors for Beauveria felina (Chung et al, 2013) and Chaetomium indicum . Marine-derived fungi are also potential metabolite producers using the OSMAC method, for example, the fungus Spicaria elegans for the production of cytochalasins (Lin et al, 2009;Wang et al, 2011) and the fungus Ascotricha sp.…”

Cyclodepsipeptides and Other O-Containing Heterocyclic Metabolites from Beauveria felina EN-135, a Marine-Derived Entomopathogenic Fungus

“…The marine-derived fungal species Beauveria felina , which is poorly described, has proven to be a rich source of various cyclodepsipeptides, such as the destruxin, isaridin, and isariin classes, as well as polyketides and terpenoids [2,3,4,5]. As part of our efforts toward the investigation of bioactive secondary metabolites of marine-derived fungi [6,7,8,9,10], Beauveria felina EN-135, an entomopathogenic fungus isolated from a marine bryozoan, attracted our attention because of the strong brine-shrimp lethality of the culture extract.…”