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Combining Metabolic Engineering and Lipid Droplet Storage Engineering for Improved α-Bisabolene Production in Yarrowia Lipolytica
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-07-18 , DOI: 10.1021/acs.jafc.3c02472 Zhihui Lu 1 , Yaping Wang 1 , Zhuo Li 1 , Yahui Zhang 1 , Sicheng He 1 , Ziyuan Zhang 1 , Susanna Leong 2 , Adison Wong 2 , Cui-Ying Zhang 1 , Aiqun Yu 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-07-18 , DOI: 10.1021/acs.jafc.3c02472 Zhihui Lu 1 , Yaping Wang 1 , Zhuo Li 1 , Yahui Zhang 1 , Sicheng He 1 , Ziyuan Zhang 1 , Susanna Leong 2 , Adison Wong 2 , Cui-Ying Zhang 1 , Aiqun Yu 1
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Bisabolene is a bioactive sesquiterpene with a wide range of applications in food, cosmetics, medicine, and aviation fuels. Microbial production offers a green, efficient, and sustainable alternative. In this study, we focused on improving the titers of α-bisabolene in Yarrowia lipolytica by applying two strategies, (i) optimizing the metabolic flux of α-bisabolene biosynthetic pathway and (ii) sequestering α-bisabolene in lipid droplet, thus alleviating its inherent toxicity to host cells. We showed that overexpression of DGA1 and OLE1 to increase lipid content and unsaturated fatty acid levels was essential for boosting the α-bisabolene synthesis when supplemented with auxiliary carbon sources. The final engineered strain Po1gαB10 produced 1954.3 mg/L α-bisabolene from the waste cooking oil under shake flask fermentation, which was 96-fold higher than the control strain Po1gαB0. At the time of writing, our study represents the highest reported α-bisabolene titer in the engineered Y. lipolytica cell factory. This work describes novel strategies to improve the bioproduction of α-bisabolene that potentially may be applicable for other high-value terpene products.
中文翻译：
结合代谢工程和脂滴储存工程提高解脂耶氏酵母的 α-红没药烯产量
红没药烯是一种生物活性倍半萜，在食品、化妆品、医药和航空燃料中具有广泛的应用。微生物生产提供了一种绿色、高效、可持续的替代方案。在本研究中，我们重点通过应用两种策略来提高解脂耶氏酵母中α-红没药烯的效价，（i）优化α-红没药烯生物合成途径的代谢通量和（ii）将α-红没药烯隔离在脂滴中，从而减轻其对宿主细胞的固有毒性。我们发现，当补充辅助碳源时，DGA1和OLE1的过度表达以增加脂质含量和不饱和脂肪酸水平对于促进 α-红没药烯合成至关重要。最终的工程菌株Po1gαB10在摇瓶发酵下从废食用油中产生了1954.3 mg/L α-红没药烯，是对照菌株Po1gαB0的96倍。在撰写本文时，我们的研究代表了工程化解脂耶氏酵母细胞工厂中报道的最高 α-红没药烯效价。这项工作描述了改善 α-红没药烯生物生产的新策略，可能适用于其他高价值萜烯产品。
更新日期：2023-07-18
中文翻译：
结合代谢工程和脂滴储存工程提高解脂耶氏酵母的 α-红没药烯产量
红没药烯是一种生物活性倍半萜，在食品、化妆品、医药和航空燃料中具有广泛的应用。微生物生产提供了一种绿色、高效、可持续的替代方案。在本研究中，我们重点通过应用两种策略来提高解脂耶氏酵母中α-红没药烯的效价，（i）优化α-红没药烯生物合成途径的代谢通量和（ii）将α-红没药烯隔离在脂滴中，从而减轻其对宿主细胞的固有毒性。我们发现，当补充辅助碳源时，DGA1和OLE1的过度表达以增加脂质含量和不饱和脂肪酸水平对于促进 α-红没药烯合成至关重要。最终的工程菌株Po1gαB10在摇瓶发酵下从废食用油中产生了1954.3 mg/L α-红没药烯，是对照菌株Po1gαB0的96倍。在撰写本文时，我们的研究代表了工程化解脂耶氏酵母细胞工厂中报道的最高 α-红没药烯效价。这项工作描述了改善 α-红没药烯生物生产的新策略，可能适用于其他高价值萜烯产品。
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