文献类型：期刊文献

英文题名：High-Level Production of Sesquiterpene Patchoulol in Saccharomyces cerevisiae

作者：Liu, Min[1];Lin, Yang-Chen[1];Guo, Jiao-Jiao[1];Du, Meng-Meng[1];Tao, Xinyi[1];Gao, Bei[1];Zhao, Ming[1];Ma, Yushu[1];Wang, Feng-Qing[1];Wei, Dong-Zhi[1]

机构：[1]East China Univ Sci & Technol, Newworld Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2021

卷号：10

期号：1

起止页码：158

外文期刊名：ACS SYNTHETIC BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000643603000015)】；

基金：This study was funded by the National Natural Science Foundation of China (No. 21776075), the Natural Science Foundation of Shanghai (No. 19ZR1473000), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering.

语种：英文

外文关键词：patchoulol; physiological status; metabolic engineering; Saccharomyces cerevisiae; sesquiterpene; cell factories

摘要：Patchoulol is a tricyclic sesquiterpene widely used in perfumes and cosmetics. Herein, comprehensive engineering strategies were employed to construct an efficient yeast strain for patchoulol production. First, a platform strain was constructed via pathway modification. Second, three off-pathway genes were deleted, which led to significant physiological changes in yeast. Further, strengthening of the ergosterol pathway, enhancement of the energy supply, and a decrease in intracellular reactive oxygen species were implemented to improve the physiological status of yeast, demonstrating a new promotive relationship between ergosterol biosynthesis and synthesis of patchoulol. Moreover, patchoulol synthase was improved through protein modification and Mg2+ addition, reaching a final titer of 141.5 mg/L in a shake flask. Finally, a two-stage fermentation with dodecane addition was employed to achieve the highest production (1632.0 mg/L, 87.0 mg/g dry cell weight, 233.1 mg/L/d) ever reported for patchoulol in a 5 L bioreactor. This work lays a foundation for green and efficient patchoulol production.