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Article

Engineering of Saccharomyces cerevisiae for 24-Methylene-Cholesterol Production

1
School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China
2
School of Life Sciences, Shanghai University, Shanghai 200444, China
*
Author to whom correspondence should be addressed.
Biomolecules 2021, 11(11), 1710; https://doi.org/10.3390/biom11111710
Submission received: 30 September 2021 / Revised: 8 November 2021 / Accepted: 15 November 2021 / Published: 17 November 2021

Abstract

24-Methylene-cholesterol is a necessary substrate for the biosynthesis of physalin and withanolide, which show promising anticancer activities. It is difficult and costly to prepare 24-methylene-cholesterol via total chemical synthesis. In this study, we engineered the biosynthesis of 24-methylene-cholesterol in Saccharomyces cerevisiae by disrupting the two enzymes (i.e., ERG4 and ERG5) in the yeast’s native ergosterol pathway, with ERG5 being replaced with the DHCR7 (7-dehydrocholesterol reductase) enzyme. Three versions of DHCR7 originating from different organisms—including the DHCR7 from Physalis angulata (PhDHCR7) newly discovered in this study, as well as the previously reported OsDHCR7 from Oryza sativa and XlDHCR7 from Xenopus laevis—were assessed for their ability to produce 24-methylene-cholesterol. XlDHCR7 showed the best performance, producing 178 mg/L of 24-methylene-cholesterol via flask-shake cultivation. The yield could be increased up to 225 mg/L, when one additional copy of the XlDHCR7 expression cassette was integrated into the yeast genome. The 24-methylene-cholesterol-producing strain obtained in this study could serve as a platform for characterizing the downstream enzymes involved in the biosynthesis of physalin or withanolide, given that 24-methylene-cholesterol is a common precursor of these chemicals.
Keywords: 24-methylene-cholesterol; campesterol; 7-dehydrocholesterol reductase 24-methylene-cholesterol; campesterol; 7-dehydrocholesterol reductase

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MDPI and ACS Style

Yang, J.; Li, C.; Zhang, Y. Engineering of Saccharomyces cerevisiae for 24-Methylene-Cholesterol Production. Biomolecules 2021, 11, 1710. https://doi.org/10.3390/biom11111710

AMA Style

Yang J, Li C, Zhang Y. Engineering of Saccharomyces cerevisiae for 24-Methylene-Cholesterol Production. Biomolecules. 2021; 11(11):1710. https://doi.org/10.3390/biom11111710

Chicago/Turabian Style

Yang, Jiao, Changfu Li, and Yansheng Zhang. 2021. "Engineering of Saccharomyces cerevisiae for 24-Methylene-Cholesterol Production" Biomolecules 11, no. 11: 1710. https://doi.org/10.3390/biom11111710

APA Style

Yang, J., Li, C., & Zhang, Y. (2021). Engineering of Saccharomyces cerevisiae for 24-Methylene-Cholesterol Production. Biomolecules, 11(11), 1710. https://doi.org/10.3390/biom11111710

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