| Title: | Systematic Engineering to Enhance 8-Hydroxygeraniol Production in Yeast |
| Author(s): | Wang H; Jiang G; Liang N; Dong T; Shan M; Yao M; Wang Y; Xiao W; Yuan Y; |
| Address: | "Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Georgia Tech Shenzhen Institute, Tianjin University, Shenzhen 518071, China" |
| ISSN/ISBN: | 1520-5118 (Electronic) 0021-8561 (Linking) |
| Abstract: | "8-Hydroxygeraniol, an important component of insect sex pheromones and defensive secretions, can be used as a potential biological insect repellent in agriculture. Microbial production provides sustainable and green means to efficiently gain 8-hydroxygeraniol. The conversion of geraniol to 8-hydroxygeraniol by P450 geraniol-8-hydroxylase (G8H) was regarded as the bottleneck for 8-hydroxygeraniol production. Herein, an integrated strategy consisting of the fitness between G8H and cytochrome P450 reductase (CPR), endoplasmic reticulum (ER) engineering, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply is implemented to enhance the production of 8-hydroxygeraniol in Saccharomyces cerevisiae. The titer of 8-hydroxygeraniol was gradually increased by 2.1-fold (up to 158.1 mg/L). Moreover, dehydrogenase ADH6 and reductase ARI1 responsible for the reduction of 8-hydroxygeraniol toward shunt products were also deleted, elevating 8-hydroxygeraniol production to 238.9 mg/L at the shake flask level. Consequently, more than 1.0 g/L 8-hydroxygeraniol in S. cerevisiae was achieved in 5.0 L fed-batch fermentation by a carbon restriction strategy, which was the highest-reported titer in microbes so far. Our work not only provides a sustainable way for de novo biosynthesis of 8-hydroxygeraniol but also sets a good reference in P450 engineering in microbes" |
| Keywords: | *Saccharomyces cerevisiae/genetics *Metabolic Engineering Terpenes 8-hydroxygeraniol NADPH supplementation P450 Saccharomyces cerevisiae endoplasmic reticulum engineering synthetic biology; |
| Notes: | "MedlineWang, Herong Jiang, Guozhen Liang, Nan Dong, Tianyu Shan, Mengying Yao, Mingdong Wang, Ying Xiao, Wenhai Yuan, Yingjin eng 2023/03/02 J Agric Food Chem. 2023 Mar 15; 71(10):4319-4327. doi: 10.1021/acs.jafc.2c09028. Epub 2023 Mar 1" |
