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Improving the production of squalene-type triterpenoid 2,3;22,23-squalene dioxide by optimizing the expression of CYP505D13 in Saccharomyces cerevisiae.
Journal of Bioscience and Bioengineering ( IF 2.3 ) Pub Date : 2020-05-15 , DOI: 10.1016/j.jbiosc.2020.04.005
Yubo Fang 1 , Mingyu Luo 2 , Xin Song 1 , Ying Shen 2 , Han Xiao 1
Affiliation  

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.



中文翻译:

通过优化CYP505D13在酿酒酵母中的表达来提高角鲨烯型三萜2,3; 22,23-角鲨烯二氧化物的生产。

角鲨烯型三萜类化合物(STs)的有效生物生产由于其重要的生物活性而备受关注。在先前的研究中,我们构建了能够产生三个ST的重组酿酒酵母。4,8-二羟基-22,23-氧化角鲨烯(ST-1),8-羟基-2,3; 22,23-角鲨烯二氧化物(ST-2)和2,3; 22,23-角鲨烯二氧化物(ST -3)。在这里,我们首先评估了这些ST对人类非小细胞肺癌(NSCLC)细胞生长的影响,发现与其他两个ST相比,ST-3表现出最大的功效。为了进一步提高ST-3的生物产量,我们采用了一种可调系统来平衡灵芝酿酒酵母细胞色素P450基因CYP505D13酿酒酵母中的表达,显着提高了ST-3的生产效价。发酵62小时后,最有效的菌株产生了78.61 mg / L的ST-3,比我们先前的研究高6.43倍。本研究表明ST-3有效抑制NSCLC细胞的增殖,并提供其有效的生物生产的见解。

更新日期:2020-05-15
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