Biosynthesis of a Functional Human Milk Oligosaccharide, 2'-Fucosyllactose, and l-Fucose Using Engineered Saccharomyces cerevisiae

Jing Jing Liu, Suryang Kwak, Panchalee Pathanibul, Jae Won Lee, Sora Yu, Eun Ju Yun, Hayoon Lim, Kyoung Heon Kim, Yong Su Jin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

2'-fucosyllactose (2-FL), one of the most abundant human milk oligosaccharides (HMOs), has received much attention due to its health-promoting activities, such as stimulating the growth of beneficial gut microorganisms, inhibiting pathogen infection, and enhancing the host immune system. Consequently, large quantities of 2-FL are on demand for food applications as well as in-depth investigation of its biological properties. Biosynthesis of 2-FL has been attempted primarily in Escherichia coli, which might not be the best option to produce food and cosmetic ingredients due to the presence of endotoxins on the cell surface. In this study, an alternative route to produce 2-FL via a de novo pathway using a food-grade microorganism,  Saccharomyces cerevisiae, has been devised. Specifically, heterologous genes, which are necessary to achieve the production of 2-FL from a mixture of glucose and lactose, were introduced into S. cerevisiae. When the lactose transporter (Lac12), de novo GDP-l-fucose pathway (consisting of GDP-d-mannose-4,6-dehydratase (Gmd) and GDP-4-keto-6-deoxymannose-3,5-epimerase-4-reductase (WcaG)), and α1,2-fucosyltransferase (FucT2) were introduced, the resulting engineered strain (D452L-gwf) produced 0.51 g/L of 2-FL from a batch fermentation. In addition, 0.41 g/L of l-fucose was produced when α-l-fucosidase was additionally expressed in the 2-FL producing strain (D452L-gwf). To our knowledge, this is the first report of 2-FL and l-fucose production in engineered S. cerevisiae via the de novo pathway. This study provides the possibility of producing HMOs by a food-grade microorganism S. cerevisiae and paves the way for more HMO production in the future.

Original languageEnglish
Pages (from-to)2529-2536
Number of pages8
JournalACS Synthetic Biology
Volume7
Issue number11
DOIs
Publication statusPublished - 2018 Nov 16

Keywords

  • 2′-fucosyllactose
  • de novo pathway
  • l-fucose
  • Saccharomyces cerevisiae
  • α-l-fucosidase

ASJC Scopus subject areas

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

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