Vitamin A Production by Engineered Saccharomyces cerevisiae from Xylose via Two-Phase in Situ Extraction

Liang Sun, Suryang Kwak, Yong Su Jin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2131-2140
Number of pages10
JournalACS synthetic biology
Volume8
Issue number9
DOIs
StatePublished - Sep 20 2019

Keywords

  • Saccharomyces cerevisiae
  • in situ extraction
  • vitamin A
  • xylose
  • β-carotene

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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