Stimulatory effect of ethanol on libertellenone H biosynthesis by Arctic fungus Eutypella sp. D-1
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Libertellenone H (1) was a promising antitumor diterpenoid isolated from Arctic fungus Eutypella sp. D-1, however, its production was very limited. In this study, we investigated the effects of ethanol on cell growth and libertellenone H production. The mycelium in ethanol-feeding cultures was fragmented and dispersed, and the titer of libertellenone H was remarkably increased to 4.88 mg l−1 in an optimal feeding manner, which was 16.4-fold higher than the control group. To provide an insight into the cell response to ethanol, genes critical to the libertellenone H biosynthesis were successfully cloned and their transcription levels were determined. The results suggested that the gene transcription levels of 3-hydroxy-3-methyl glutaric acyl coenzyme A reductase and geranylgeranyl diphosphate synthase were up-regulated by ethanol stimulation. The results from this study were helpful for further understanding of the ethanol function on diterpenes biosynthesis as well as developing more effective strategies for over-production of these desired secondary metabolites.
KeywordsArctic fungus Libertellenone H Ethanol feeding 3-Hydroxy-3-methyl glutaric acyl coenzyme A reductase Geranylgeranyl diphosphate synthase
This work was financially supported by the National High Technology Research and Development Program of China (2012AA092105) and the Fundamental Research Funds for the Central Universities (22A201514040). We thank Prof. Xiaoyu Liu, the Second Military Medical University for supply of the strain and the libertellenone H standard.
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