TY - JOUR
T1 - Enhancing oleanolic acid production in engineered Saccharomyces cerevisiae
AU - Zhao, Yujia
AU - Fan, Jingjing
AU - Wang, Chen
AU - Feng, Xudong
AU - Li, Chun
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/6
Y1 - 2018/6
N2 - Oleanolic acid is a plant-derived pentacyclic triterpenoid compound with various biological activities. Recently, biosynthesis of oleanolic acid in microbes has been demonstrated as a promising and green way, but the production is too low for industrialization. To improve oleanolic acid production, this study constructed a novel pathway for biosynthesis of oleanolic acid in Saccharomyces cerevisiae by improving the pairing efficiency between cytochrome P450 monooxygenase and reductase. Furthermore, to improve the transcriptional efficiency of heterologous genes, the cellular galactose regulatory network was reconstructed by knocking out galactose metabolic genes GAL80 and GAL1. Finally, the 3-hydroxy-3-methylglutaryl-CoA reductase, squalene synthase and 2,3-oxidosqualene synthase were further overexpressed, increasing oleanolic acid production up to 186.1 ± 12.4 mg/L in flask shake. Combined with fermentation optimization, the final oleanolic acid production was 606.9 ± 9.1 mg/L with a yield of 16.0 ± 0.8 mg/g DCW which was 7.6-fold higher than the reported maximum production.
AB - Oleanolic acid is a plant-derived pentacyclic triterpenoid compound with various biological activities. Recently, biosynthesis of oleanolic acid in microbes has been demonstrated as a promising and green way, but the production is too low for industrialization. To improve oleanolic acid production, this study constructed a novel pathway for biosynthesis of oleanolic acid in Saccharomyces cerevisiae by improving the pairing efficiency between cytochrome P450 monooxygenase and reductase. Furthermore, to improve the transcriptional efficiency of heterologous genes, the cellular galactose regulatory network was reconstructed by knocking out galactose metabolic genes GAL80 and GAL1. Finally, the 3-hydroxy-3-methylglutaryl-CoA reductase, squalene synthase and 2,3-oxidosqualene synthase were further overexpressed, increasing oleanolic acid production up to 186.1 ± 12.4 mg/L in flask shake. Combined with fermentation optimization, the final oleanolic acid production was 606.9 ± 9.1 mg/L with a yield of 16.0 ± 0.8 mg/g DCW which was 7.6-fold higher than the reported maximum production.
KW - Galactose metabolic network
KW - Oleanolic acid
KW - Oxidation-reduction system
UR - http://www.scopus.com/inward/record.url?scp=85042917443&partnerID=8YFLogxK
U2 - 10.1016/j.biortech.2018.02.096
DO - 10.1016/j.biortech.2018.02.096
M3 - Article
C2 - 29526355
AN - SCOPUS:85042917443
SN - 0960-8524
VL - 257
SP - 339
EP - 343
JO - Bioresource Technology
JF - Bioresource Technology
ER -
