工程改造的解脂耶氏酵母菌株中麦角固醇产量的提高。
Improved campesterol production in engineered Yarrowia lipolytica strains.
作者信息
Zhang Yu, Wang Ying, Yao Mingdong, Liu Hong, Zhou Xiao, Xiao Wenhai, Yuan Yingjin
机构信息
Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, 92 Weijin Road, Tianjin, 300072, China.
SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
出版信息
Biotechnol Lett. 2017 Jul;39(7):1033-1039. doi: 10.1007/s10529-017-2331-4. Epub 2017 Mar 29.
OBJECTIVES
To engineer Yarrowia lipolytica for improving the heterologous production of campesterol (a key precursor to manufacture pharmaceutical steroids).
RESULTS
By screening 7-dehydrocholesterol reductase (DHCR7) from diverse species, DHCR7 from Danio rerio was the best candidate for campesterol synthesis. Overexpression of ACL (ATP: citrate lyase) or POX2 (peroxisome acyl-CoA oxidase 2) were key to improving campesterol production. The highest yield of campesterol was 942 mg/l was with the strain overexpressing POX2 in a 5 l bioreactor via high cell density fermentation process with a restricted supply of carbon sourc, sunflower seed oil.
CONCLUSIONS
A promising platform to synthesize downstream steroid drugs was established. Efficient approaches were provided to improve the production of desired molecules in Y. lipolytica with high oil utilization efficiency.
目的
对解脂耶氏酵母进行工程改造，以提高菜油甾醇（制造药用类固醇的关键前体）的异源产量。
结果
通过筛选来自不同物种的7-脱氢胆固醇还原酶（DHCR7），斑马鱼的DHCR7是菜油甾醇合成的最佳候选酶。ACL（ATP：柠檬酸裂解酶）或POX2（过氧化物酶体酰基辅酶A氧化酶2）的过表达是提高菜油甾醇产量的关键。在5升生物反应器中，通过高细胞密度发酵工艺，以向日葵籽油作为受限碳源供应，过表达POX2的菌株获得的菜油甾醇最高产量为942毫克/升。
结论
建立了一个有前景的合成下游甾体药物的平台。提供了有效的方法来提高解脂耶氏酵母中所需分子的产量，并具有高油脂利用效率。
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