Abstract
One strain-many compounds (OSMAC) manipulation of the sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 resulted in the production of new secondary metabolites. The chemical study of the fermentation, cultivated on 3% artificial sea salt in the rice media, led to the isolation of twelve compounds, including eight new polyketide derivatives, heterocornols Q–X (1–8), one new ceramide (9), and three known analogues (10–12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data and calculated ECD analysis. Heterocornols Q (1) and R (2) are novel 6/5/7/5 tetracyclic polyketide derivatives featuring dihydroisobenzofuran and benzo-fused dioxabicyclo [4.2.1] nonane system, which might be derived from the acetyl-CoA by epoxidation, polyene cyclization, and rearrangement to form the core skeleton. Compound 12 showed moderate or weak antimicrobial activities against with MIC values ranging from 25 to 100 μg/mL. Heterocornols T and X (7 and 8) could inhibit the production of LPS-induced NO significantly, comparable to dexamethasone. Further Western blotting analysis showed 7 and 8 markedly suppressed the iNOS protein expression in LPS-induced RAW 264.7 cells in a dose-dependent manner. The result showed that 7 and 8 might serve as potential leads for development of anti-inflammatory activity.
Highlights
During the past several decades, marine-derived fungi are recognized as an important source of novel drug leads
In order to enlarge the diversity of metabolites, different strategies such as the one strain-many compounds (OSMAC) strategy [1,2,3,4,5], epigenetic modification [6,7,8], and genome mining have been devoted to activating the silent gene clusters [9,10,11,12,13]
Our previous investigation on the marine sponge-derived fungus Pestalotiopsis heterocornis XWS03F09 has resulted in the discovery of heterocornols A–P [14,15], pestaloisocoumarins A and B, isopolisin B, and pestalotiol A [16]
Summary
During the past several decades, marine-derived fungi are recognized as an important source of novel drug leads. Most of their biosynthetic gene clusters are silent under laboratory conditions fungi, whereas only a fraction of gene clusters have been transcribed. In order to enlarge the diversity of metabolites, different strategies such as the one strain-many compounds (OSMAC) strategy [1,2,3,4,5], epigenetic modification [6,7,8], and genome mining have been devoted to activating the silent gene clusters [9,10,11,12,13]. For exploring the chemical diversity of microorganisms using the OSMAC strategy, we reinvestigated the secondary metabolites of the strain XWS03F09, with additional 3% artificial sea salt to solid rice medium
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