Roberts Tom L, Dolan Jonathan P, Miller Gavin J, Lima Marcelo A D, Cosgrove Sebastian C
Lennard-Jones Laboratory, School of Chemical & Physical Sciences, Keele University Keele Staffordshire ST5 5BG UK
Centre for Glycoscience, Keele University Keele Staffordshire ST5 5BG UK
React Chem Eng. 2025 May 9. doi: 10.1039/d5re00127g.
We report here the continuous flow synthesis of a high-value sugar nucleotide. Immobilisation of enzymes onto solid carriers permitted transfer of the biocatalysts into packed bed reactors to realise a continuous biocatalytic platform for the synthesis of uridine diphosphate -acetylglucosamine (UDP-GlcNAc) on 100 mg scale, with capacity for multiple reuses. The modular continuous flow approach described here represents a significant, up to 11-fold, improvement in space time yield (STY) when compared to batch studies, along with preventing product induced enzyme inhibition, reducing the need for an additional enzyme to break down inorganic pyrophosphate (PPi). The modular nature of the system has also allowed tailored conditions to be applied to each enzyme, overcoming issues relating to thermal stability. This development presents a platform approach towards a more efficient, continuous synthesis of important glycan targets including glycoproteins, specific oligosaccharide sequences and glycosylated drug targets.
我们在此报告一种高价值糖核苷酸的连续流动合成方法。将酶固定在固体载体上，使得生物催化剂能够转移到填充床反应器中，从而实现了一个连续的生物催化平台，可在100毫克规模上合成尿苷二磷酸 - N - 乙酰葡糖胺（UDP-GlcNAc），并且具有多次重复使用的能力。与分批研究相比，此处描述的模块化连续流动方法在时空产率（STY）方面有显著提高，高达11倍，同时还能防止产物诱导的酶抑制，减少了对额外用于分解无机焦磷酸（PPi）的酶的需求。该系统的模块化性质还允许对每种酶应用定制条件，克服了与热稳定性相关的问题。这一进展为更高效、连续地合成重要聚糖靶标（包括糖蛋白、特定寡糖序列和糖基化药物靶标）提供了一种平台方法。
