Enhancing Geranylgeraniol Production by Metabolic Engineering and Utilization of Isoprenol as a Substrate in Saccharomyces cerevisiae

The amount of geranylgeranyl diphosphate (GGPP) is vital for microbial production of geranylgeraniol (GGOH) in Saccharomyces cerevisiae. In this study, a GGPP synthase with stronger catalytic ability was used to increase the supply of GGPP, and an engineered strain producing 374.02 mg/L GGOH at the...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2021-04, Vol.69 (15), p.4480-4489
Main Authors: Wang, Junhua, Zhu, Linghuan, Li, Youran, Xu, Sha, Jiang, Wei, Liang, Chaojuan, Fang, Yakun, Chu, Alex, Zhang, Liang, Ding, Zhongyang, Shi, Guiyang
Format: Article
Language:English
Subjects:
Biofuels and Biobased Materials
Diterpenes
Metabolic Engineering
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - genetics
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Summary:The amount of geranylgeranyl diphosphate (GGPP) is vital for microbial production of geranylgeraniol (GGOH) in Saccharomyces cerevisiae. In this study, a GGPP synthase with stronger catalytic ability was used to increase the supply of GGPP, and an engineered strain producing 374.02 mg/L GGOH at the shake flask level was constructed. Then, by increasing the metabolic flux of the mevalonate (MVA) pathway and the supply of isopentenyl pyrophosphate (IPP), the titer was further increased to 772.98 mg/L at the shake flask level, and we achieved the highest GGOH titer to date of 5.07 g/L in a 5 L bioreactor. This is the first report on the utilization of isoprenol for increasing the amount of IPP and enhancing GGOH production in S. cerevisiae. In the future, these strategies and engineered strains can be used to enhance the production of other terpenoids in S. cerevisiae.
ISSN:0021-8561
1520-5118
DOI:10.1021/acs.jafc.1c00508