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Engineering Saccharomyces cerevisiae for high yield production of α-amyrin via synergistic remodeling of α-amyrin synthase and expanding the storage pool.

Authors
  • Yu, Yuan1
  • Rasool, Aamir2
  • Liu, Haoran2
  • Lv, Bo2
  • Chang, Pengcheng2
  • Song, Hao3
  • Wang, Ying4
  • Li, Chun5
  • 1 Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Institute for Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, 5 South Zhong Guancun Street, Beijing, PR China; College of Life Sciences, North China University of Science and Technology, 21 Bo Hai Road, Tangshan, PR China. , (China)
  • 2 Institute for Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, 5 South Zhong Guancun Street, Beijing, PR China. , (China)
  • 3 Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China. , (China)
  • 4 Institute for Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, 5 South Zhong Guancun Street, Beijing, PR China. Electronic address: [email protected] , (China)
  • 5 Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Institute for Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, 5 South Zhong Guancun Street, Beijing, PR China; School of Life Science, Yan'an University, Shaanxi, 716000, PR China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Metabolic engineering
Publication Date
Aug 22, 2020
Volume
62
Pages
72–83
Identifiers
DOI: 10.1016/j.ymben.2020.08.010
PMID: 32841679
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

α-Amyrin is a plant-originated high-valued triterpene that is highly effective against several pathological ailments. α-Amyrin production by engineered Saccharomyces cerevisiae has been achieved by introducing α-amyrin synthase (αAS). However, the low yield of α-amyrin highly limits its industrial application; the low catalytic activity of αAS and the toxic effect of α-amyrin have been considered key elements. In this study, the highest yield of α-amyrin was obtained in engineered S. cerevisiae by remodeling α-amyrin synthase MdOSC1 and expanding the storage pool. The yield of α-amyrin was increased to 11-fold higher than that of the control by the triple mutant MdOSC1N11T/P250H/P373A obtained based on the modeling analysis. Furthermore, key genes of MVA pathway were overexpressed to provide sufficient precursors, and DGA1 (Diacylglycerol acyltransferase) was overexpressed to expand the intracellular storage capacity. Finally, the as-constructed aAM12 strain produced 213.7 ± 12.4 mg/L α-amyrin in the shake flask and 1107.9 ± 76.8 mg/L in fed-batch fermentation; the fermentation yield was 106-fold higher than that of the original aAM1 strain under the same conditions, representing the highest α-amyrin yield in yeast reported to date. Microbial production of α-amyrin with over 1 g/L will be suitable for commercialization and can accelerate the industrial production of α-amyrin in yeast. Copyright © 2020 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

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