Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation, identification, and fermentation conditions optimization for camptothecin production

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• 作者：Xiang Pu ; Xixing Qu ; Fei Chen ; Jinku Bao…
• 关键词：Camptothecin ; Endophytic fungi ; Trichoderma atroviride LY357 ; Fermentation ; Elicitor ; Adsorbent resin
• 刊名：Applied Microbiology and Biotechnology
• 出版年：2013
• 出版时间：November 2013
• 年：2013
• 卷：97
• 期：21
• 页码：9365-9375
• 全文大小：519KB
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• 作者单位：Xiang Pu (1) (2) (4)
  Xixing Qu (1) (4)
  Fei Chen (1) (4)
  Jinku Bao (2)
  Guolin Zhang (1)
  Yinggang Luo (1) (3)
  
  1. Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, People’s Republic of China
  2. College of Life Sciences, Sichuan University, Chengdu, 610064, People’s Republic of China
  4. University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China
  3. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, People’s Republic of China
  
• ISSN：1432-0614

文摘

Camptothecin (CPT), the third largest anticancer drug, is produced mainly by Camptotheca acuminata and Nothapodytes foetida. CPT itself is the starting material for clinical CPT-type drugs, but the plant-derived CPT cannot support the heavy demand from the global market. Research efforts have been made to identify novel sources for CPT. In this study, three CPT-producing endophytic fungi, Aspergillus sp. LY341, Aspergillus sp. LY355, and Trichoderma atroviride LY357, were isolated and identified from C. acuminata. Most CPT produced by these fungi was found in the fermentation broth, and their corresponding CPT yields were 7.93, 42.92, and 197.82?μg?l?, respectively. The CPT-producing capability of LY341 and LY355 was completely lost after repeat subculturing. A substantial decrease of CPT production was also observed in the second generation of LY357. However, a stable and sustainable production of CPT was found from the second generation through the eighth generation of LY357. The fermentation medium, time, pH, temperature, and agitation rate were optimized for CPT production. Methyl jasmonate and XAD16 were proven to be an optimum elicitor and adsorbent resin, respectively, in view of that CPT yield was increased 3.4- and 11-fold through their use. A 50- to 75-fold increase of CPT yield was obtained when the optimized fermentation conditions, elicitor, and adsorbent resin were combined and applied to the culture of the seventh and eighth generations of LY357, and the highest CPT yield was 142.15?μg?l?. The CPT-producing T. atroviride LY357 paves a potential to uncover the mysteries of CPT biosynthesis.