Creating the Future of Nutrition with Human Milk Oligosaccharides (HMOs) Production

HMOs are complex mixed oligosaccharides naturally occurring in human milk, which are powerful in promoting population health. CD BioGlyco specializes in research on glycobiology, and we utilize efficient synthetic biology methods to provide our clients with high-quality HMO production services.

HMOs Production Service by Synthetic Biology Technology at CD BioGlyco

Microbial method

The microbial method we offer focuses on the production of HMOs by metabolically engineered microorganisms. The host strains we offer include but are not limited to, Escherichia coli, Saccharomyces cerevisiae, and Bacillus subtilis. E. coli is the most commonly used microorganism for the production of HMOs in single-cell media. Saccharomyces cerevisiae and Bacillus subtilis are food-grade microbial hosts with a better safety profile, which facilitates the production of HMOs in the food and pharmaceutical industries.

We obtain genetically engineered bacteria that can synthesize HMOs efficiently by using bacteria as the starting strains, introducing relevant genes in the product synthesis pathway, and reconstructing their metabolic networks through genetic engineering techniques. Then, HMOs are obtained by microbial fermentation and purification, and so on.

We construct the synthetic pathway of HMO in the microbial host by rational design and optimal reconstruction of the de novo and salvage pathways. In the fermenter, we produce HMOs in microbial hosts using several methods to enhance the transport of substrate monosaccharides (e.g., overexpression of glcP and lac12 genes), remove the hydrolysis pathway of monosaccharides (e.g., knockdown of the yesZ gene), and introduce key genes of the de novo and salvage pathways. In addition, we use a high-copy-number plasmid to overexpress the genes involved in the de novo pathway-related genes to enhance the production efficiency of HMO. For the obtained HMO, we use mass spectrometry and fluorescence detector for detection and porous graphitized carbon, capillary electrophoresis, and liquid chromatography for separation and purification.

Enzyme method

The synthesis of HMO involves various key enzymes, such as guanosine diphosphate (GDP) mannose 4,6-hydratase (Gmd), GDP fucose synthetase (GFS), α-1,2-fucosyltransferase (FucT2), and so on. We produce HMOs in a three-step enzymatic process using GDP-D-mannose or lactose as starting substrates. First, we catalyze the synthesis of GDP-4-keto-6-deoxymannose from GDP-D-mannose using the Gmd. Next, we utilize the GFS to catalyze the synthesis of GDP-fucose from GDP-4-keto-6-deoxymannose. Finally, we catalyze the synthesis of HMO using FucT2 to synthesize GDP-fucose and lactose. Further, we provide an anion-exchange column for desalting the obtained HMO and a gel column for purifying the HMO, which in turn improves the quality of the HMO.

Applications

• HMO is a major component of human milk, and the production of HMO can be used in the development of infant formula.
• HMO stimulates the production of immune substances and antibodies in the intestines and enhances cellular activity. Therefore, HMO can be used to develop drugs that enhance human immunity.
• The production of HMOs can be used in the development of antiviral drugs. HMOs can act as soluble receptors for viruses against a wide range of viral pathogens by reducing viral adhesion to target cells.

Advantages

• We are equipped with state-of-the-art synthetic biology technologies to provide our clients with efficient and safe HMO production services.
• We provide custom HMO production solutions according to our client's research purposes.
• We not only provide large-scale production of HMOs but also provide detailed production report interpretation and data analysis for our clients.

CD BioGlyco is dedicated to research in the field of glycobiology and has extensive experience in synthetic biology, providing comprehensive HMO production services to each of our clients. If you are interested in our services, please feel free to contact us.

• Carbohydrate Antigen Production Service
• Natural Glycan Production Service
• Bioactive Ingredient Production Service
• Specific Glycan Molecule Production Service