Production of sesquiterpenoid zerumbone from metabolic engineered Saccharomyces cerevisiae

Metabolic Engineering
Chuanbo ZhangWenyu Lu

Abstract

Zerumbone, the predominant sesquiterpenoid component of Zingiber zerumbet, exhibits diverse pharmacological properties. In this study, de novo production of zerumbone was achieved in a metabolically engineered yeast cell factory by introducing α-humulene synthase (ZSS1), α-humulene 8-hydroxylase (CYP71BA1) and zerumbone synthase variant (ZSD1S114A) from Z. zerumbet, together with AtCPR1 from Arabidopsis thaliana into the yeast strain. Multistep metabolic engineering strategies were applied, including the over-expression of the mevalonate (MVA) pathway rate-limiting enzymes tHMG1 and ERG20, regulation of ERG9 by an inducible promoter and competitive pathway deletion to redirect metabolic flux toward the desired product. In the engineered strain, α-humulene production increased by 18-fold, to 92 mg/L compared to that in the original strain. Five cytochrome P450 reductases (CPRs) from different sources were selected for CYP71BA1 adaptability tests, and AtCPR1 from A. thaliana was found to be the optimal, producing 113.16 μg/L of 8-hydroxy-α-humulene. Multicopy integration of CYP71BA1, AtCPR1, ZSS1 and ICE2 (type III membrane protein) genes resulting in strain LW14 increased the production of 8-hydroxy-α-humulene by 134-fold to 15....Continue Reading

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Citations

Sep 25, 2019·Microbial Cell Factories·Chuanbo ZhangWenyu Lu
May 12, 2020·Frontiers in Bioengineering and Biotechnology·Caizhe Zhang, Kui Hong
May 28, 2019·Applied Microbiology and Biotechnology·Sandra Moser, Harald Pichler
May 16, 2020·Trends in Biochemical Sciences·Giovanna Di Nardo, Gianfranco Gilardi
Mar 27, 2021·Current Opinion in Biotechnology·Chuanteng MaGuojian Zhang
Aug 12, 2021·Journal of Agricultural and Food Chemistry·Jie MaiXiao-Jun Ji
Jul 10, 2019·Journal of Agricultural and Food Chemistry·Bin MaFeng-Qing Wang
Jan 17, 2020·Journal of Agricultural and Food Chemistry·Chuanbo ZhangWenyu Lu
Nov 19, 2020·Journal of Agricultural and Food Chemistry·Meijie LiJianming Yang
Nov 10, 2021·Journal of Agricultural and Food Chemistry·Qi GuoHe Huang

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