(−)-α-Bisabolol is a natural monocyclic sesquiterpene alcohol present in German chamomile and has been used as an ingredient of functional foods, cosmetics and pharmaceuticals. In this study, metabolic engineering strategies were attempted to produce (−)-α-bisabolol in Saccharomyces cerevisiae. The codon-optimized MrBBS gene coding for (−)-α-bisabolol synthase from Matricaria recutita was expressed in S. cerevisiae for (−)-α-bisabolol production. The resulting strain (DM) produced 9.5 mg/L of (−)-α-bisabolol in 24 h of batch culture. Additionally, the mevalonate pathway was intensified by introducing a truncated HMG1 gene coding for HMG-CoA reductase and ERG10 encoding acetyl-CoA thiolase. The resulting strain (DtEM) produced a 2.9-fold increased concentration of (−)-α-bisabolol than the DM strain. To increase the acetyl-CoA pool, the ACS1 gene coding for acetyl-CoA synthetase was also overexpressed in the DtEM strain. Finally, the DtEMA strain produced 124 mg/L of (−)-α-bisabolol with 2.7 mg/L-h of productivity in a fed-batch fermentation, which were 13 and 6.8 times higher than the DM strain in batch culture, respectively. Conclusively, these metabolically-engineered approaches might pave the way for the sustainable production of other sesquiterpenes in engineered S. cerevisiae.

(-)-α-红没药醇是存在于德国洋甘菊中的天然单环倍半萜醇，已被用作功能性食品、化妆品和药品的成分。在这项研究中，尝试使用代谢工程策略在酿酒酵母中生产 (-)-α-没药醇。编码来自Matricaria recutita 的(-)-α-红没药醇合酶的密码子优化的MrBBS基因在酿酒酵母中表达，用于 (-)-α-红没药醇生产。所得菌株 (DM) 在 24 小时分批培养中产生 9.5 mg/L (-)-α-没药醇。此外，通过引入编码 HMG-CoA 还原酶和ERG10的截短的HMG1基因来强化甲羟戊酸途径编码乙酰辅酶A硫解酶。所得菌株 (DtEM) 产生的 (-)-α-没药醇浓度比 DM 菌株高 2.9 倍。为了增加乙酰辅酶A库，编码乙酰辅酶A合成酶的ACS1基因也在DtEM菌株中过表达。最后，DtEMA 菌株在补料分批发酵中产生 124 mg/L 的 (-)-α-没药醇，生产率为 2.7 mg/Lh，分别比分批培养中的 DM 菌株高 13 倍和 6.8 倍。最后，这些代谢工程方法可能为在工程酿酒酵母中可持续生产其他倍半萜铺平道路。