TY - JOUR
T1 - Vitamin A Production by Engineered Saccharomyces cerevisiae from Xylose via Two-Phase in Situ Extraction
AU - Sun, Liang
AU - Kwak, Suryang
AU - Jin, Yong Su
N1 - Funding Information:
This work was funded by the DOE Center for Advanced Bioenergy and Bioproducts Innovation (U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research under Award Number DE-SC0018420). Any opinions, findings, and conclusions or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the U.S. Department of Energy. L.S. would like to thank the China Scholarship Council (CSC) for financial support (File No. 201606350094). The authors thank Christine Atkinson for her diligent proofreading of this paper.
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/9/20
Y1 - 2019/9/20
N2 - Vitamin A is an essential human micronutrient and plays critical roles in vision, reproduction, immune system, and skin health. Current industrial methods for the production of vitamin A rely on chemical synthesis from petroleum-derived substrates, such as acetone and acetylene. Here, we developed a biotechnological method for production of vitamin A from an abundant and nonedible sugar. Specifically, we engineered Saccharomyces cerevisiae to produce vitamin A from xylose - the second most abundant sugar in plant cell wall hydrolysates - by introducing a β-carotene biosynthetic pathway, and a gene coding for β-carotene 15,15′-dioxygenase (BCMO) into a xylose-fermenting S. cerevisiae. The resulting yeast strain produced vitamin A from xylose at a titer 4-fold higher than from glucose. When a two-phase in situ extraction strategy with dodecane or olive oil as an extractive agent was employed, vitamin A production improved additional 2-fold. Furthermore, a xylose fed-batch fermentation with dodecane in situ extraction achieved a final titer of 3350 mg/L vitamin A, which consisted of retinal (2094 mg/L) and retinol (1256 mg/L). These results suggest that potential limiting factors of vitamin A production in yeast, such as insufficient supply of isoprenoid precursors, and limited intracellular storage capacity, can be effectively addressed by using xylose as a carbon source, and two-phase in situ extraction. The engineered S. cerevisiae and fermentation strategies described in this study might contribute to sustainable and economic production of vitamin A, and vitamin A-enriched bioproducts from renewable biomass.
AB - Vitamin A is an essential human micronutrient and plays critical roles in vision, reproduction, immune system, and skin health. Current industrial methods for the production of vitamin A rely on chemical synthesis from petroleum-derived substrates, such as acetone and acetylene. Here, we developed a biotechnological method for production of vitamin A from an abundant and nonedible sugar. Specifically, we engineered Saccharomyces cerevisiae to produce vitamin A from xylose - the second most abundant sugar in plant cell wall hydrolysates - by introducing a β-carotene biosynthetic pathway, and a gene coding for β-carotene 15,15′-dioxygenase (BCMO) into a xylose-fermenting S. cerevisiae. The resulting yeast strain produced vitamin A from xylose at a titer 4-fold higher than from glucose. When a two-phase in situ extraction strategy with dodecane or olive oil as an extractive agent was employed, vitamin A production improved additional 2-fold. Furthermore, a xylose fed-batch fermentation with dodecane in situ extraction achieved a final titer of 3350 mg/L vitamin A, which consisted of retinal (2094 mg/L) and retinol (1256 mg/L). These results suggest that potential limiting factors of vitamin A production in yeast, such as insufficient supply of isoprenoid precursors, and limited intracellular storage capacity, can be effectively addressed by using xylose as a carbon source, and two-phase in situ extraction. The engineered S. cerevisiae and fermentation strategies described in this study might contribute to sustainable and economic production of vitamin A, and vitamin A-enriched bioproducts from renewable biomass.
KW - Saccharomyces cerevisiae
KW - in situ extraction
KW - vitamin A
KW - xylose
KW - β-carotene
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U2 - 10.1021/acssynbio.9b00217
DO - 10.1021/acssynbio.9b00217
M3 - Article
C2 - 31374167
AN - SCOPUS:85071729101
SN - 2161-5063
VL - 8
SP - 2131
EP - 2140
JO - ACS Synthetic Biology
JF - ACS Synthetic Biology
IS - 9
ER -