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XU Rui, LI Xiaoming, XU Gangming, WANG Bingui. Optimizing production of asperolide A, a potential anti-tumor tetranorditerpenoid originally produced by the algal-derived endophytic fungus Aspergillus wentii EN-48[J]. Journal of Oceanology and Limnology, 2017, 35(3): 658-663

Optimizing production of asperolide A, a potential anti-tumor tetranorditerpenoid originally produced by the algal-derived endophytic fungus Aspergillus wentii EN-48

XU Rui1,2, LI Xiaoming1, XU Gangming1, WANG Bingui1
1 Laboratory of Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China;
2 University of Chinese Academy of Sciences, Beijing 100049, China
The marine algal-derived endophytic fungus Aspergillus wentii EN-48 produces the potential anti-tumor agent asperolide A, a tetranorlabdane diterpenoid active against lung cancer. However, the fermentation yield of asperolide A was very low and only produced in static cultures. Static fermentation conditions of A. wentii EN-48 were optimized employing response surface methodology to enhance the production of asperolide A. The optimized conditions resulted in a 13.9-fold yield enhancement, which matched the predicted value, and the optimized conditions were successfully used in scale-up fermentation for the production of asperolide A. Exogenous addition of plant hormones (especially 10 μmol/L methyl jasmonate) stimulated asperolide A production. To our knowledge, this is first optimized production of an asperolide by a marine-derived fungus. The optimization is effective and valuable to supply material for further anti-tumor mechanism studies and preclinical evaluation of asperolide A and other norditerpenoids.
Key words:    Aspergillus wentii|asperolide A|anti-tumor agent|fermentation optimization   
Received: 2016-02-01   Revised: 2016-03-31
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