SynBio Research Platform , Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300072 , People's Republic of China.
J Agric Food Chem. 2019 Mar 6;67(9):2581-2588. doi: 10.1021/acs.jafc.9b00009. Epub 2019 Feb 22.
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.
化合物 K（CK）是一种罕见的四环三萜类化合物，具有重要的医学特性，如抗肿瘤和抗炎活性。在此，首次在代谢工程化的解脂耶氏酵母中构建了 CK 的高效生物合成途径，工程菌株 YL-CK0 产生了 5.1mg/L 的 CK。通过过表达 MVA 途径中的关键基因并融合细胞色素 P450 单加氧酶（PPDS）和 NADPH-P450 还原酶，CK 的产量进一步提高了 5.96 倍，达到 30.4mg/L。最后，通过在 5L 发酵罐中使用菌株 YL-MVA-CK 进行分批补料发酵，获得了 161.8mg/L 的 CK 产量。据我们所知，这是在解脂耶氏酵母中异源 CK 合成的最高产量的首次报道。本研究证明了利用解脂耶氏酵母作为平台生产高价值三萜类化合物的可行性。
