Bioactive Sesquiterpene Aryl Esters from the Culture Broth of <i>Armillaria</i> sp.

Kobori, Hajime; Sekiya, Atsushi; Suzuki, Tomohiro; Choi, Jae-Hoon; Hirai, Hirofumi; Kawagishi, Hirokazu

doi:10.1021/np500322t

Cited by 33 publications

(29 citation statements)

References 21 publications

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“…However, in the case of the melleolides, the physiological reason for introducing a chlorine atom is unclear. Available studies on structure-activity relationships do not support strongly changed bioactivity through chlorination (8,9,20). Hence, a role in detoxification of melleolides through halogenation also cannot be assumed, and the reason why A. mellea secures chlorination of its toxic natural products to the degree described here remains elusive.…”

Section: Discussionmentioning

confidence: 83%

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A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins

Wick

Heine

Lackner

et al. 2016

Appl Environ Microbiol

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The basidiomycetous tree pathogen Armillaria mellea (honey mushroom) produces a large variety of structurally related antibiotically active and phytotoxic natural products, referred to as the melleolides. During their biosynthesis, some members of the melleolide family of compounds undergo monochlorination of the aromatic moiety, whose biochemical and genetic basis was not known previously. This first study on basidiomycete halogenases presents the biochemical in vitro characterization of five flavin-dependent A. mellea enzymes (ArmH1 to ArmH5) that were heterologously produced in Escherichia coli. We demonstrate that all five enzymes transfer a single chlorine atom to the melleolide backbone. A 5-fold, secured biosynthetic step during natural product assembly is unprecedented. Typically, flavin-dependent halogenases are categorized into enzymes acting on free compounds as opposed to those requiring a carrier-protein-bound acceptor substrate. The enzymes characterized in this study clearly turned over free substrates. Phylogenetic clades of halogenases suggest that all fungal enzymes share an ancestor and reflect a clear divergence between ascomycetes and basidiomycetes.

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Section: Discussionmentioning

confidence: 83%

“…The melleolides are intriguing, as they show two distinct structure-activity relationships for their cytotoxic and antifungal bioactivities (8). Phytotoxic activities have also been established (9,10). Further, the melleolides represent one of the largest fungal natural product families with more than 60 structural variants.…”

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confidence: 99%

A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins

Wick

Heine

Lackner

et al. 2016

Appl Environ Microbiol

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“…The isolated meroterpenes were identified as melleolide C [10] (2), H [11] (3) and J [21] (4), melledonal C [12] (5), 10-hydroxymelleolide [15] (6), armillarin [22] (7), and armillaridin [25] (8) by means of mass spectrometry and NMR spectroscopy, while methyl linoleate (9) was identified by NMR spectroscopy. 13-Hydroperoxyarmillarinin (1) displayed a peak at m/z 503.1443 [M + Na + ] + (δ = − 0.040 ppm) in the HRESIMS in the positive mode, corresponding to a molecular formula of C 24 H 29 ClO 8 and identical to melledonal C. The NMR spectra of 1 and 5 showed strong similarities, but, in contrast to 5, substance 1 possessed just one hydroxymethylene group at δ H 5.60 (t, 8.7 Hz, H-5).…”

Section: Resultsmentioning

confidence: 99%

“…Sesquiterpene aryl esters from Armillaria sp. were already found to possess antibacterial [10,16], antifungal [28] and cytotoxic [29,30] effects and to inhibit the growth of lettuce [25]. Inhibition of degranulation of RBL-2H3 cells was observed for the first time in A. ostoyae, and all purified compounds were also isolated from the mycelium of A. ostoyae for the first time.…”

Section: Discussionmentioning

confidence: 95%

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2017

PMIO

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IntroductionDuring our investigations of biologically active fungi, Armillaria ostoyae (Romagn.) Herink [1], a basidiomycete belonging to the family Physalacriaceae, came into focus, as it affected degranulation in RBL-2H3 cells. The species is commonly known as edible mushroom, but it also occurs as a devastating pathogen of various tree species causing serious economic losses in forestry all over the world [2]. The mechanisms of host infection as well as hostpathogen interactions have been studied intensively [3][4][5][6][7]. In addition, Armillaria mushrooms attract a wider interest, for instance, as the worldʼs biggest living organism [8] or as a producer of bioluminescence [9]. A broad variety of antibacterial and cytotoxic sesquiterpene aryl esters were isolated from the genus Armillaria, especially Armillaria mellea [10][11][12][13][14][15][16][17][18][19][20], but also Armillaria novae-zelandiae [21] and Armillaria tabescens [22]. In this manuscript, degranulation inhibiting effects of extracts from fruiting bodies and cultivated mycelium as well as bioactivity-guided isolation of compounds from the mycelium of A. ostoyae are described. Degranulation is the process in which cells release secretory products stored in secretory granules by exocytosis. It is an important feature of many immune cells, e.g., for release of mediators [23]. Inhibition of degranulation can result in the blocking of inflammatory or allergic reactions.

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“…Aryl ketones, benzoate esters, and benzamides are ubiquitous structures found in natural and biologically active compounds (e.g., hypericin [1-3], acetosyringone [4,5], oxcarbazepine [6,7], daidzein [8,9], sitaxentan [10,11], radicicol [12,13], arnamial [14][15][16], epicatechingallate [17], Rucaparib [18][19][20][21], and Leucine-rich repeat kinase-2 (LRRK2) [22,23], Figure 1). In addition, such carbonyl compounds are also extensively used in advanced materials [24][25][26][27][28] and as key intermediates for the synthesis of fine chemicals, including structurally complex compounds.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Homogeneous Metal-Catalyzed Aerobic C–H Oxidation of Benzylic Compounds

et al. 2018

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Csp 3 -H oxidation of benzylic methylene compounds is an established strategy for the synthesis of aromatic ketones, esters, and amides. The need for more sustainable oxidizers has encouraged researchers to explore the use of molecular oxygen. In particular, homogeneous metal-catalyzed aerobic oxidation of benzylic methylenes has attracted much attention. This account summarizes the development of this oxidative strategy in the last two decades, examining key factors such as reaction yields, substrate:catalyst ratio, substrate scope, selectivity over other oxidation byproducts, and reaction conditions including solvents and temperature. Finally, several mechanistic proposals to explain the observed results will be discussed. relevant parameters such as reaction yields, substrate:catalyst ratio, selectivity towards target carbonyl compounds, reaction media, and other experimental conditions. Considering that metal complexes and combination of metal salts and ligands have been described as catalysts or precatalysts in this field, this review is organized according to the metal core involved in the reaction. Although mechanism for this transformation is far from being completely elucidated, several proposals will be discussed. Catalysts 2018, 8, x FOR PEER REVIEW 2 of 21Following the pioneering works by Ishii [63-66], cobalt(II) salts combined with N-hydroxyphtalimide (NHPI) derivatives have been amply used for the aerobic C-H oxidation of methylene compounds at atmospheric pressure. An in situ-generated phthalimide-N-oxyl radical (PINO) is proposed to play a key catalytic role as hydrogen atom abstracting species in the reaction, and other N-hydroxylated ligand/additives prone to form related radical species have also been evaluated and compared with NHPI. Among other transition metals, cobalt salts have been defined as promoters Catalysts 2018, 8, 640 3 of 21for the formation of PINO. Nolte and coworkers published the use of 0.5 mol% of Co(OAc) 2 ·4H 2 O combined with NHPI (10 mol%) in acetic acid to perform benzylic oxidation of 2-(hetero)arylacetic esters to the corresponding α-ketoesters at relatively low temperatures (40-80 • C). Lower yields (<30%) were obtained from some o-alkoxylated and brominated substrates, as well as from all the heteroaromatic esters. Finally, with regard to the oxidation of ethylbenzene to acetophenone, several N-hydroxy-phthalimides were evaluated as co-catalysts, achieving good conversion rates (except for nitro-substituted NHPIs) and relatively good acetophenone:1-phenylethanol ratios (59-88:2-5) [94].The solvent-free oxidation of several alkylbenzenes to the corresponding ketones using di-n-decyl-di-methyl ammonium bromide (DDAB) and other phase transfer agents was explored by Patil et al. A 0.5 mol% of the latter quaternary ammonium salt was required along with NHPI (3 mol%) and CoCl 2 ·6H 2 O (1 mol%) to perform the oxidation under oxygen gas flow rate of 110 mL/min at 65 • C, although other metal sources (MnCl 2 (H 2 O) 4 and CrCl 3 (H 2 O) 6 ) and ammonium phase transfer catal...

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Bioactive Sesquiterpene Aryl Esters from the Culture Broth of Armillaria sp.

Cited by 33 publications

References 21 publications

A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins

A Fivefold Parallelized Biosynthetic Process Secures Chlorination of Armillaria mellea (Honey Mushroom) Toxins

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Recent Advances in Homogeneous Metal-Catalyzed Aerobic C–H Oxidation of Benzylic Compounds

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