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Biosynthesis of ursolic acid and oleanolic acid in Saccharomyces cerevisiae
Author(s) -
Lu Chunzhe,
Zhang Chuanbo,
Zhao Fanglong,
Li Dashuai,
Lu Wenyu
Publication year - 2018
Publication title -
aiche journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.958
H-Index - 167
eISSN - 1547-5905
pISSN - 0001-1541
DOI - 10.1002/aic.16370
Subject(s) - oleanolic acid , ursolic acid , fermentation , biochemistry , saccharomyces cerevisiae , chemistry , yeast , chromatography , medicine , alternative medicine , pathology
Ursolic acid and oleanolic acid are pentacyclic triterpenoid compounds with a variety of biological activities. A mixture of ursolic acid and oleanolic acid has higher antitumor activity than the individual acids. We have developed a simultaneous biosynthesis pathway for different proportions of ursolic acid and oleanolic acid in Saccharomyces cerevisiae . The ScLCZ08 strain produced 175.15 mg/L of the ursolic acid precursor α‐amyrin, the highest amount reported. Ursolic and oleanolic acid titers and proportions were optimized using Medicago truncatula amyrin C‐28 oxidase and Arabidopsis thaliana cytochrome P450 reductase. Using glucose and ethanol fed‐batch fermentation strategies, the final ursolic acid and oleanolic acid titers were 123.27 and 155.58 mg/L, respectively, demonstrating 4.77‐fold and 4.95‐fold higher production than the parent strain. The ScLCZ11 strain displayed the highest ursolic acid production obtained via microbial fermentation in fed‐batch culture to date. © 2018 American Institute of Chemical Engineers AIChE J , 64: 3794–3802, 2018