Global Metabolic Rewiring of Yeast Enables Overproduction of Sesquiterpene (+)-Valencene
Global Metabolic Rewiring of Yeast Enables Overproduction of Sesquiterpene (+)-Valencene
复制标题
DOI：
10.1021/acs.jafc.2c01394
复制
发表时间：
2022-06-15
影响因子：
6.1
通讯作者：
Zhou, Yongjin J.
中科院分区：
文献类型：
--
作者：
Cao, Chunyang;Cao, Xuan;Zhou, Yongjin J.
（+）-朱栾倍半萜是一种生物活性倍半萜，可用于调味和香料，微生物生产提供了一种替代的可持续途径。然而，细胞代谢的复杂性使其高水平生产具有挑战性。在这里，我们报告了全球重新布线细胞代谢从头生产（+）-朱栾倍半萜在酵母酿酒酵母工程中心代谢，甲羟戊酸途径，和倍半萜合酶。特别是，我们表明，代谢转化可以帮助加速菌株的建设过程和多拷贝表达的倍半萜合酶是必不可少的，以提高前体供应的产品合成的代谢通量。该工程菌在摇瓶补料分批发酵条件下的（+）-朱栾倍半萜产量为1.2 g/L，比出发菌株提高了549倍，显示了酵母细胞工厂生产（+）-朱栾倍半萜的巨大潜力。
(+)-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 de novo production of (+)-valencene in yeast Saccharomyces cerevisiae 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.