Xu Rui, Xu Gang-Ming, Li Xiao-Ming, Li Chun-Shun, Wang Bin-Gui
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Nanhai Road 7, Qingdao 266071, China.
College of Earth Science, University of Chinese Academy of Sciences, Yuquan Road 19A, Beijing 100049, China.
Mar Drugs. 2015 Nov 19;13(11):7040-54. doi: 10.3390/md13117040.
The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.
潜在的抗肿瘤药物文蒂内酯由新分离的海洋真菌双态曲霉产生。这种真菌源自深海沉积物,并通过多相方法进行鉴定,该方法结合了表型、分子和次生代谢产物谱。然而,仅在静态培养下检测到文蒂内酯的产生,且产量极低。为了提高文蒂内酯的产量,使用响应面法对培养条件进行了优化。在最佳静态发酵条件下,实验值与预测模型密切一致。文蒂内酯A和B的产量分别提高了约11倍,达到13.4 mg/L和6.5 mg/L。通过扩大文蒂内酯生产的发酵规模进一步验证了该结果。此外,发现一些小分子诱导剂具有刺激文蒂内酯产生的能力。据我们所知,这是首次报道由深海来源的海洋真菌优化生产四环降蒈二萜类化合物。本研究可能对文蒂内酯的高效生产以及去甲二萜类化合物抗肿瘤机制的基础研究具有重要价值。