National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Liaoning Province Collaborative Innovation Center for Marine Food Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, People's Republic of China.
Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, People's Republic of China.
J Agric Food Chem. 2022 Jun 15;70(23):7180-7187. doi: 10.1021/acs.jafc.2c01394. Epub 2022 Jun 3.
(+)-Valencene is a bioactive sesquiterpene that can be used for flavoring and fragrances, and microbial production provides an alternative sustainable access. However, the complexity of cellular metabolism makes it challenging for its high-level production. Here, we report the global rewiring cellular metabolism for production of (+)-valencene in yeast by engineering central metabolism, mevalonate pathway, and sesquiterpenoid synthase. In particular, we show that metabolic transformation can help accelerate the strain construction process and multiple copy expression of sesquiterpenoid synthase is essential for boosting the metabolic flux for product synthesis with enhanced supply of precursors. The engineered strain produced 1.2 g/L (+)-valencene under fed-batch fermentation in shake flasks, which was increased by 549-fold and demonstrated great potential of the yeast cell factory for (+)-valencene production.
(+)-柠檬烯是一种具有生物活性的倍半萜烯，可用于调味和香料，微生物生产为其提供了一种可持续的替代途径。然而，细胞代谢的复杂性使得其难以进行高水平生产。在这里，我们通过工程化中央代谢、甲羟戊酸途径和倍半萜合酶，报告了在酵母中生产(+)-柠檬烯的全局重布线细胞代谢。特别是，我们表明代谢转化可以帮助加速菌株构建过程，并且倍半萜合酶的多次拷贝表达对于提高产物合成的代谢通量和增强前体供应以促进 (+)-柠檬烯的合成是必不可少的。在摇瓶中的分批补料发酵中，工程化菌株生产了 1.2 g/L 的 (+)-柠檬烯，比原始菌株提高了 549 倍，展示了酵母细胞工厂在(+)-柠檬烯生产方面的巨大潜力。
