Production of Triterpene Ginsenoside Compound K in the Non-conventional Yeast Yarrowia lipolytica
Production of Triterpene Ginsenoside Compound K in the Non-conventional Yeast Yarrowia lipolytica
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非常规解脂耶氏酵母生产三萜人参皂苷化合物K
DOI：
10.1021/acs.jafc.9b00009
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发表时间：
2019-03-06
影响因子：
6.1
通讯作者：
Lu, Wenyu
中科院分区：
文献类型：
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作者：
Li, Dashuai;Wu, Yufen;Lu, Wenyu
化合物K（CK）是一种稀有的四环三萜类化合物，具有重要的药理活性，如抗肿瘤和抗炎活性。本研究首次在代谢工程菌Yarrowia lipolytica中构建了CK的高效生物合成途径，工程菌YL-CK 0的CK产量为5.1 mg/L。随着MVA途径关键基因的过表达以及细胞色素P450单加氧酶（PPDS）和NADPH-P450还原酶的融合，CK的产量进一步增加了5.96倍，达到30.4 mg/L。最后，在5L发酵罐中进行补料分批发酵，发酵液中CK的含量达到161.8mg/L。据我们所知，这是第一次报道异源CK合成的最高滴度在Y。解脂本研究证明了利用Y. lipolytica作为平台。
Compound K (CK) is a rare, tetracyclic, triterpenoid compound with important medical properties, such as antitumor and anti-inflammatory activities. Herein, an efficient biosynthetic pathway of CK was constructed in metabolically engineered Yarrowia lipolytica for the first time, and the engineered strain, YL-CK0, produced 5.1 mg/L CK. The production of CK was further increased by 5.96-fold to 30.4 mg/L with overexpression of key genes in the MVA pathway and fusion of cytochrome P450 monooxygenase (PPDS) and NADPH-P450 reductase. Finally, 161.8 mg/L CK production was achieved by fed-batch fermentation in a 5 L fermenter using the strain YL-MVA-CK. To the best of our knowledge, this is the first report on heterologous CK synthesis with the highest titer in Y. lipolytica. This study demonstrates the feasibility of producing high-value triterpenoid compounds using Y. lipolytica as a platform.