Research Progress on the Synthesis Methods of Human Milk Oligosaccharides

Boxin Qiao; Lei Liu; Jinlei Rong; Enxu Wang

doi:10.62051/ijphmr.v2n1.22

Authors

Boxin Qiao
Lei Liu
Jinlei Rong
Enxu Wang

DOI:

https://doi.org/10.62051/ijphmr.v2n1.22

Keywords:

Human milk oligosaccharides, Chemical synthesis, Enzymatic synthesis, Microbial fermentation

Abstract

Human milk oligosaccharides are the third largest solid component in breast milk and have functions such as regulating the intestinal flora, inhibiting the growth of pathogens, influencing the immune response of infants, and promoting brain development. Currently, the synthesis methods of human milk oligosaccharides include chemical synthesis, enzymatic synthesis and microbial fermentation. Chemical synthesis has low efficiency and doubts about product safety; enzymatic synthesis has a high conversion rate, but the substrate cost is high and the enzyme activity is unstable. Microbial fermentation can use Escherichia coli, yeast, Bacillus subtilis and Corynebacterium glutamicum as chassis strains, but it is not possible to determine the pros and cons of the research on chassis strains. At present, many kinds of human milk oligosaccharides have been approved by many countries as food additives or new raw materials and have application potential in many fields.

References

[1] Zhu Y, Wan L, Li W, et al. Recent advances on 2′-fucosyllactose: physiological properties, applications, and production approaches [J]. CriticalReviews in Food Science and Nutrition, 2022, 62(8): 2083-2092.

[2] Bode L. Human milk oligosaccharides: Every baby needs a sugar mama [J]. Glycobiology, 2012, 22(9): 1147-62.

[3] Grollman A P, Hall C W, Ginsburg V. Biosynthesis of Fucosyllactose and Other Oligosaccharides Found in Milk [J]. Journal of Biological Chemistry, 1965, 240(3): 975-981.

[4] Sprenger G A, Baumgartner F, Albermann C. Production of human milk oligosaccharides by enzymatic and whole-cell microbial biotransformations [J]. Journal of Biotechnology, 2017, 258:79-91.

[5] Anderson A, Donald A S R. Improved method for the isolation of 2′-fucosyllactose from human milk [J]. Journal of Chromatography A, 1981, 211(1): 170-174.

[6] Nolan L S, Rimer J M, Good M. The role of human milk oligosaccharides and probiotics on the neonatal microbiome and risk of necrotizing enterocolitis: a narrative review. Nutrients, 2020, 12(10): 3052.

[7] Iribarren C, Magnusson M K, Vigsnaes L K, et al. The effects of human milk oligosaccharides on gut microbiota, metabolite profiles and host mucosal response in patients with irritable bowel syndrome [J]. Nutrients, 2021, 13(11): 3836.

[8] Spicer S K, Gaddy J A, Townsend S D. Recent advances on human milk oligosaccharide antimicrobial activity [J]. Current Opinion in Chemical Biology, 2022, 71: 102-202.

[9] Lin A E, Autran C A, Szyszka A, et al. Human milk oligosaccharides inhibit growth of group B Streptococcus [J]. Journal of Biological Chemistry, 2017, 292(27): 11243-11249.

[10] Donovan S M. Human milk oligosaccharides-the plot thickens [J]. The British Journal of Nutrition, 2009, 101(9): 1267-1269.

[11] Kawashima N, Yoon S J, Itoh K, et al. Tyrosine kinase activity of epidermal growth factor receptor is regulated by GM3 binding through carbohydrate to carbohydrate interactions [J]. The Journal of Biological Chemistry, 2009, 284(10): 6147-6155.

[12] Bode L. The functional biology of human milk oligosaccharides [J]. Early Human Development, 2015, 91(11): 619-622.

[13] Andersson B, Porras O, Hanson L A, et al. Inhibition of attachment of Streptococcus pneumoniae and Haemophilus influenzae by human milk and receptor oligosaccharides [J]. The Journal of infectious diseases, 1986, 153(2): 232-237.

[14] Hanson L A. Breast-feeding and immune function [J]. Proceedings of the Nutrition Society, 2007, 66(3): 384-396.

[15] He Y, Liu S, Kling DE et al. The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation [J]. Gut, 2016, 65: 33-46.

[16] Wang B. Sialic acid is an essential nutrient for brain development and cognition [J]. Annual Review of Nutrition, 2009, 29(1): 177-222.

[17] Wang B, Brand - Miller J. The role and potential of sialic acid in human nutrition [J]. European journal of clinical nutrition, 2003, 57(11): 1351-1369.

[18] Marriage B j, Buck R H, Goehring K C, et al. Infants fed a lower calorie formula with 2′-FL show growth and 2′-FL uptake like breast-fed infants [J]. Journal of Pediatric Gastroenterology and Nutrition, 2015, 61(6): 649-658.

[19] Murata T, Inukai T, Suzuki M, et al. Facile enzymatic conversion of lactose into lacto-N-tetraose and lacto-N-neotetraose [J]. Glycoconjugate Journal, 1999, 16: 189-195.

[20] Miermont A., Zeng Y., Jing Y., et al. Syntheses of LewisX and dimeric LewisX: Construction of branched oligosaccharides by a combination of preactivation and reactivity based chemoselective one-pot glycosylations [J]. Journal of Organic Chemistry, 2007, 72 (23): 8958-8961.

[21] Karl F Johnson Synthesis of oligosaccharides by bacterial enzymes [J]. Glycoconjugate Journal, 1999, 16 (2): 141-146.

[22] Wehmeier P U F. Synthesis of the milk oligosaccharide 2′-fucosyllactose using recombinant bacterial enzymes [J]. Carbohydrate Research, 2001, 334(2): 97-103.

[23] Parschat K, Scheriber S, Wartenberg D, et al. High-titer de novo biosynthesis of the predominant human milk oligosaccharide 2′-fucosyllactose from sucrose in Escherichia coil [J]. ACS Synth Biol, 2020, 9(10): 2784-2796.

[24] Zhang JM, Zhu YY, Zhang WL, Mu W. Efficient production of a functional human milk oligosaccharide 3'-sialyllactose in genetically engineered Escherichia coli [J]. ACS Synthetic Biology, 2022, 11(8): 2837-2845.

[25] Hu M, Li M, Li C, et al. High-level productivity of lacto-n-neotetraose in Escherichia coli by systematic metabolic engineering [J]. Journal of Agricultural and Food Chemistry, 2023, 71(9): 4051-4058.

[26] Hollands K, Baron C M, Gibson K J, et al. Engineering two species of yeast as cell factories for 2′-fucosyllactose [J]. Metabolic Engineering, 2019, 52: 232-242.

[27] Lee J W, Kwak S, Liu J J, et al. Enhanced 2'-fucosyllactose production by engineered Saccharomyces cerevisiae using xylose as a co-substrate [J]. Metablic Engineering, 2020, 62: 322-329.

[28] Ji M, Liu Y, Xie S, et al. De novo synthesis of 2'-fucosyllactose in engineered Bacillus subtilis ATCC 6051a [J]. Process Biochemistry, 2022, 120: 178-185.

[29] Dong X., Li N., Liu Z., et al. Modular pathway engineering of key precursor supply pathways for lacto-N-neotetraose production in Bacillus subtilis [J]. Biotechnology for Biofuels, 2019, 12 (1): 212.

[30] Zhang Q W, Liu Z M, Liu L, et al. Engineered bacillus subtilis for the de novo production of 2'-fucosyllactose [J]. Microbial Cell Factories, 2022, 21(1): 1-11.

[31] Lu M, Mosleh I, Abbaspourrad A. Engineered microbial routes for human milk oligosaccharides synthesis [J]. ACS Synthetic Biology, 2021, 10(5): 923-938.

[32] WENG Ruru, WEI Xinhui, LI Haozheng, et al. Progress in Microbial Synthesis of 2'-Fucosyllactose [J]. Food Science, 20221, 42(17): 248-254.

[33] Chin YW, Park JB, Park YC, et al. Metabolic engineering of Corynebacterium glutamicum to produce GDP-L-fucose from glucose and mannose. Bioprocess Biosyst Eng. 2013; 36(6):749-756.

[34] Seo J-H, Chin Y-W, Jo H-Y. Method of producing 2′-fucosyllactose using Corynebacterium glutamicum [P]. US Patent, 20180298389A1. 2018.

[35] Zhang Q W, Wu Y K, Gong M Y, et al. Production of proteins and commodity chemicals using engineered Bacillus subtilis platform strain. Essays in Biochemistry, 2021, 65(2): 173-185.