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Recent advances and challenges in microbial production of human milk oligosaccharides

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Abstract

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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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (31871784, 31870069, 21676119 and 31671845), the National Key Research and Development Program of China (2018YFA0900300).

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  1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Jieying Deng, Xueqin Lv, Guocheng Du & Long Liu

  2. Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Jianghua Li & Jian Chen

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  1. Jieying Deng
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JYD collected the information and wrote the manuscript, XQL and LL revised the manuscript, and LL, JHL, GCD and JC conceived the project.

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Deng, J., Lv, X., Li, J. et al. Recent advances and challenges in microbial production of human milk oligosaccharides. Syst Microbiol and Biomanuf 1, 1–14 (2021). https://doi.org/10.1007/s43393-020-00004-w

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