期刊
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
卷 130, 期 3, 页码 265-271出版社
SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2020.04.005
关键词
Squalene-type triterpenoid; 2,3;22,23-Squalene dioxide; CYP505D13; Non-small cell lung cancer; Saccharomyces cerevisiae
资金
- National Key R&D Program of China [2018YFA0900600]
- National Natural Science Foundation of China [31971344, 31600071]
- Shanghai Municipal Natural Science Foundation [17ZR1448900, 18ZR1420300]
- Interdisciplinary Program of Shanghai Jiao Tong University [YG2017MS82]
- Construction Project of High Level Local Universities in Shanghai and Pharmacy [XD18011]
- DaSilva Award (The Society for Biotechnology, Japan)
The efficient bioproduction of squalene-type triterpenoids (STs) has attracted considerable attention due to their significant biological activities. In a previous study, we constructed a recombinant Saccharomyces cerevisiae capable of producing three STs; 4,8-dihydroxy-22,23-oxidosqualene (ST-1), 8-hydroxy-2,3;22,23-squalene dioxide (ST-2), and 2,3;22,23-squalene dioxide (ST-3). Here, we first evaluated the effects of these STs on the growth of human non-small cell lung cancer (NSCLC) cells, and found that ST-3 exhibited the greatest potency compared to the other two STs. To further enhance the bioproduction of ST-3, we adopted a tunable system to balance the expression of the Ganoderma lucidum cytochrome P450 gene CYP505D13 in S. cerevisiae, which significantly improved the ST-3 production titer. The most effective strain produced 78.61 mg/L of ST-3 after 62 h fermentation, which was 6.43 times higher than that of our previous study. The present study demonstrated that ST-3 effectively inhibits the proliferation of NSCLC cells, and provides insight into its efficient bioproduction. (C) 2020, The Society for Biotechnology, Japan. All rights reserved.
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