Substrate and Process Engineering for Biocatalytic Synthesis and Facile Purification of Human Milk Oligosaccharides. Issue 9 (18th February 2022)

• Record Type: Journal Article
• Authors: Bai, Yuanyuan; Yang, Xiaohong; Yu, Hai; Chen, Xi
• Is Part Of: ChemSusChem. Volume 15:Issue 9(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-18
• Subjects: biocatalysis -- carbohydrates -- chemoenzymatic synthesis -- glycosylation -- oligosaccharides; Green chemistry -- Periodicals; Sustainable engineering -- Periodicals; Chemistry -- Periodicals; Chemical engineering -- Periodicals; 660
• DOI: 10.1002/cssc.202102539
• Languages: English
• ISSNs: 1864-5631

Abstract

Abstract: Innovation in process development is essential for applying biocatalysis in industrial and laboratory production of organic compounds, including beneficial carbohydrates such as human milk oligosaccharides (HMOs). HMOs have attracted increasing attention for their potential application as key ingredients in products that can improve human health. To efficiently access HMOs through biocatalysis, a combined substrate and process engineering strategy is developed, namely multistep one‐pot multienzyme (MSOPME) design. The strategy allows access to a pure tagged HMO in a single reactor with a single C18‐cartridge purification process, despite the length of the target. Its efficiency is demonstrated in the high‐yielding (71–91 %) one‐pot synthesis of twenty tagged HMOs (83–155 mg), including long‐chain oligosaccharides with or without fucosylation or sialylation up to nonaoses from a lactoside without the isolation of the intermediate oligosaccharides. Gram‐scale synthesis of an important HMO derivative – tagged lacto‐ N ‐fucopentaose‐I (LNFP‐I) – proceeds in 84 % yield. Tag removal is carried out in high efficiency (94–97 %) without the need for column purification to produce the desired natural HMOs with a free reducing end. The method can be readily adapted for large‐scale synthesis and automation to allow quick access to HMOs, other glycans, and glycoconjugates. Abstract : Got milk sugars ? A highly efficient multistep one‐pot multienzyme (MSOPME) strategy is developed for carbohydrate synthesis by integrating biocatalysis substrate and process engineering concepts. A single C18‐cartridge purification process is sufficient for any target. The strategy is demonstrated for preparative and gram‐scale synthesis of numerous human milk oligosaccharides (HMOs), which are attractive targets for industrial biocatalytic production.