Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.
J1 Biotech Co., Ltd., Wuhan, 430075, China.
Metab Eng. 2022 Jul;72:107-115. doi: 10.1016/j.ymben.2022.03.005. Epub 2022 Mar 13.
(+)-Nootkatone is a valuable, functional sesquiterpene that is widely used in food, cosmetics, pharmaceutical, agriculture, and other fields. However, only traces of it accumulate in plants, which is insufficient to meet the market demand. Therefore, commercial (+)-nootkatone is currently synthesized from (+)-valencene. Here, we engineered Saccharomyces cerevisiae to achieve high production of (+)-valencene. Employing gene screening, protein engineering and biosynthetic pathway optimization, we achieved 12.4 g/L (+)-valencene production with the mutant strain. This titer was further increased to 16.6 g/L, the highest titer reported to date, by coupling critical factors for cell growth and biochemical pathway induction. Subsequently, (+)-nootkatone was chemically synthesized from bio-fermented (+)-valencene with a yield of 80%. This study achieved efficient microbial synthesis of (+)-valencene, which may be utilized in industrial production and stabilize the supply of (+)-nootkatone.
（+）-诺卡酮是一种有价值的功能性倍半萜烯，广泛应用于食品、化妆品、制药、农业等领域。然而，它在植物中的积累量很少，远远不能满足市场需求。因此，目前商业（+）-诺卡酮是由（+）-柠檬烯合成的。在这里，我们通过基因筛选、蛋白质工程和生物合成途径优化，使酿酒酵母实现了（+）-柠檬烯的高产。通过结合细胞生长和生物化学途径诱导的关键因素，突变株的（+）-柠檬烯产量进一步提高到 16.6g/L，这是迄今为止报道的最高产量。随后，通过化学方法从生物发酵的（+）-柠檬烯中合成（+）-诺卡酮，产率为 80%。本研究实现了（+）-柠檬烯的高效微生物合成，可用于工业生产，稳定（+）-诺卡酮的供应。
