Biotechnological Production and Bioactivities of Mollisin and Two New, Structurally Related Fungal Naphthoquinone Metabolites

Abstract

The antibiotic and fungicidal deuteromycete Mollisia caesia Sacc. was cultivated on a large scale. Mollisin (1; = 8-(dichloroacetyl)-5-hydroxy-2,7-dimethylnaphthalene-1,4-dione) and two new tri- and tetrahalogenated metabolites, mollisin A (2) and mollisin B (3) were isolated from M. caesia. The formation of 2 and 3 indicates that the biosynthesis of these compounds starts from a C(16) polyketide (Scheme). Mollisin (1) shows strong fungicidal activities against Sclerophoma pityophila (Corda) v. Höhn and Heterobasidion annosum (Fr.) Bref., which is one of the most-destructive basidiomycetes in coniferous forests. The metabolites 1-3 possess interesting pharmacological activities in assays in search of anti-inflammatory and antiproliferative drugs.

New Metabolites from the Endophytic Fungus Mollisia sp.

“…Among the isolates, ergosterol peroxide (12) inhibited NO production in activated macrophages, and emodin (8) showed IL-6 inhibitory activity; their IC 50 values were 36.99 and 5.97 PM, respectively.…”

“…In summary, only a few compounds have been reported from Mollisia species [11][12][13][14][15]. These compounds are D-methylene ketones, naphthoquinones, isocoumarins, nitriles, sesterterpenes, and zaragozic acids [11][12][13][14][15].…”

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Two new metabolites, mollisinols A and B (1 and 2), and one first isolated from nature, mollisilactone (3), along with 13 known compounds (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), were isolated from the EtOAc-soluble fraction of the solid-state fermentation of the endophytic fungus Mollisia sp., derived from the root bark of Ardisia cornudentata Mez (Myrsinaceae). Their structures were elucidated by spectroscopic analyses, including 1D and 2D NMR experiments, and by HR-ESI-MS mass spectrometry.

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“…(Dermateaceae) BCRC 09F0002, was isolated from the root bark of Ardisia cornudentata Mez (Myrsinaceae). Previous chemical investigations of the genus Mollisia have received less attention, and only a few articles have been reported [11][12][13][14][15]. In the course of our search for potentially diverse secondary metabolites from natural fungal sources, and to further understanding the minor metabolites of the genus Mollisia, we examined an EtOAc-soluble fraction of Mollisia sp., which showed inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) release and interleukin-6 (IL-6) production in RAW 264.7 murine macrophages, as determined by our primary screening (approximately 90% inhibition at a concentration of 10 Pg/mL).…”

“…In addition to the three compounds (1-3) mentioned above, the following 13 known compounds were also isolated: ilanepyrrolal (4) [17], palmitic acid (5) [18], (R)-(-)-mevalolactone (6) [19,20], chrysophanol (7) [21], emodin (8) [22], E-sitostenone (9) [23], a mixture of E-sitosterol (10) and stigmasterol (11) [24], ergosterol peroxide (12) [25], 9,11-dehydroergosterol peroxide (13) [26], 9-hydroxycerevisterol (14) [27], cerevisterol (15) [28], and (22E,24R)-ergosta-8(14),22-diene-3E,5D,6E,7D-tetrol (16) [29].…”