Engineering two species of yeast as cell factories for 2′-fucosyllactose

Hollands, Kerry; Baron, Christopher M.; Gibson, Katharine J.; Kelly, Kristen J.; Krasley, Elizabeth; Laffend, Lisa A.; Lauchli, Ryan M.; Maggio-Hall, Lori A.; Nelson, Mark J.; Prasad, Jahnavi C.; Ren, Yanping; Rice, Barbara A.; Rice, Gregory H.; Rothman, Steven C.

doi:10.1016/j.ymben.2018.12.005

“…Reported titers are up to 24 gL À1 . [72] Lacto-N-tetraose (LNT), another abundant HMO in milk, has also been produced in E. coli by an all-chromosomalexpressed strain. [73] In addition to lactose permease expression, the two glycosyltransferase genes utilized were Neisseria meningitidis lgtA,w hich encodes an b-1,3-N-acetylglucosaminyltransferase for the addition of UDP-N-acetylglucosamine to lactose to form precursor LNTII, and E. coli O55:H7 wbgO,ab-1,3-galactosyltransferase to ultimately form LNT through addition of UDP-galactose onto LNTII.…”

Section: Human Milk Oligosaccharidesmentioning

confidence: 99%

Unlocking Nature's Biosynthetic Power—Metabolic Engineering for the Fermentative Production of Chemicals

Hoff¹,

Plassmeier

²

,

Blankschien

³

et al. 2020

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Fermentation as a production method for chemicals is especially attractive, as it is based on cheap renewable raw materials and often exhibits advantages in terms of costs and sustainability. The tremendous development of technology in bioscience has resulted in an exponentially increasing knowledge about biological systems and has become the main driver for innovations in the field of metabolic engineering. Progress in recombinant DNA technology, genomics, and computational methods open new, cheaper, and faster ways to metabolically engineer microorganisms. Existing biosynthetic pathways for natural products, such as vitamins, organic acids, amino acids, or secondary metabolites, can be discovered and optimized efficiently, thereby enabling competitive commercial production processes. Novel biosynthetic routes can now be designed by the rearrangement of nature's unlimited number of enzymes and metabolic pathways in microbial strains. This expands the range of chemicals accessible by biotechnology and has yielded the first commercial products, while new fermentation technologies targeting novel active ingredients, commodity chemicals, and CO2‐fixation methods are on the horizon.

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“…Saccharomyces cerevisiae was also engineered to produce 2′-FL by introducing the salvage pathway from B. fragilis along with the lactose permease LAC12 from Kluyveromyces lactis [46]. The de novo pathway later established in Y. lipolytica increased the 2′-FL titer from 15 to 24 g/L as compared with S. cerevisiae [47,48]. The substrates' import and the cofactor supply were improved in engineered Bacillus subtilis, and 5.01 g/L 2′-FL was obtained through introducing the salvage pathway and FucT2 from H. pylori [49,50].…”

Section: The Microbial Production Of 2′-fl and 3-flmentioning

confidence: 99%

Recent advances and challenges in microbial production of human milk oligosaccharides

Deng

¹

,

Li

²

,

Du

³

et al. 2020

Syst Microbiol and Biomanuf

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Human milk oligosaccharides (HMOs) are one of the major differences between livestock milk and human milk, and the prebiotic functions of HMOs have been verified through in vitro and clinical trials. The most abundant HMOs include 2′-fucysollactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-neotetraose (LNnT) and lacto-N-tetraose (LNT); their application and synthesis have attracted wide attentions. In recent years, the biotechnological production of 2′-FL, 3-FL, LNnT and LNT have emerged based on techniques such as whole-cell catalysis and fermentation. In particular, the development of metabolic engineering and synthetic biology methods and strategies have facilitated efficient biosynthesis of these HMOs. However, these advantages have not been systematically reviewed yet. In this review, we first discuss the structures and applications of HMOs; secondly, strategies of microbial synthesis of the most abundant 2′-FL, 3-FL, LNnT and LNT are summarized and compared. Finally, challenges and perspectives of efficient microbial production of HMOs as well as strategies for overcoming the challenges are discussed. This review reveals the whole picture of recent development in HMOs microbial synthesis and can further facilitate the understanding of limiting factors, and further propose a few directions to promote the development of efficient production hosts.

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“…Recently, S. cerevisiae and Yarrowia lipolytica have been engineered and optimized in terms of lactose uptake, synthesis of GDP‐fucose, solubility of H. pylori fucosyltransferase, and suitable transporters for 2‐FL efflux. Reported titers are up to 24 g L −1 [72] …”

Section: Designing Synthetic Metabolic Pathwaysmentioning

confidence: 99%

Unlocking Nature's Biosynthetic Power—Metabolic Engineering for the Fermentative Production of Chemicals

Hoff¹,

Plassmeier

²

,

Blankschien

³

et al. 2020

View full text Add to dashboard Cite

Fermentation as a production method for chemicals is especially attractive, as it is based on cheap renewable raw materials and often exhibits advantages in terms of costs and sustainability. The tremendous development of technology in bioscience has resulted in an exponentially increasing knowledge about biological systems and has become the main driver for innovations in the field of metabolic engineering. Progress in recombinant DNA technology, genomics, and computational methods open new, cheaper, and faster ways to metabolically engineer microorganisms. Existing biosynthetic pathways for natural products, such as vitamins, organic acids, amino acids, or secondary metabolites, can be discovered and optimized efficiently, thereby enabling competitive commercial production processes. Novel biosynthetic routes can now be designed by the rearrangement of nature's unlimited number of enzymes and metabolic pathways in microbial strains. This expands the range of chemicals accessible by biotechnology and has yielded the first commercial products, while new fermentation technologies targeting novel active ingredients, commodity chemicals, and CO2‐fixation methods are on the horizon.

show abstract

Engineering two species of yeast as cell factories for 2′-fucosyllactose

Cited by 70 publications

References 57 publications

Unlocking Nature's Biosynthetic Power—Metabolic Engineering for the Fermentative Production of Chemicals

Unlocking Nature's Biosynthetic Power—Metabolic Engineering for the Fermentative Production of Chemicals

Recent advances and challenges in microbial production of human milk oligosaccharides

Unlocking Nature's Biosynthetic Power—Metabolic Engineering for the Fermentative Production of Chemicals

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