乳清中的生物活性物质：酶促生产唾液酸-N-乙酰乳糖胺的可持续方法,ACS Sustainable Chemistry & Engineering

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乳清中的生物活性物质：酶促生产唾液酸-N-乙酰乳糖胺的可持续方法
ACS Sustainable Chemistry & Engineering ( IF 7.1 ) Pub Date : 2022-04-08 , DOI: 10.1021/acssuschemeng.2c00506
Masih Karimi Alavijeh _{1,

2} , Birgitte Zeuner ₃ , Anne S. Meyer ₃ , Sally L. Gras _{1,

2} , Sandra E. Kentish ₁

Affiliation

使用乳清制造医药产品促进了可持续的环境和经济发展。这项研究代表了一种将乳清升级为 3'-唾液酸-N-乙酰乳糖胺 (3'-SLN) 作为糖蛋白的重要结构成分和能够与流感病毒血凝素形成复合物的受体类似物的新策略。N-乙酰乳糖胺 (LacNAc) 是直接从乳清中酶促生产和纯化的，无需预处理。一种工程化和重组产生的唾液酸酶，具有来自非致病性锥虫范围内的转唾液酸化能力然后用于将唾液酸从乳清衍生的唾液酸化酪蛋白糖巨肽 (CGMP) 转移到该 LacNAc。在 LacNAc 与 CGMP 中结合的唾液酸的等摩尔比下，获得了最大 0.92 mM 3'-SLN；另一方面，摩尔比为 10 的 3'-SLN 浓度增加了四倍。使用机器学习和机械方法在不同反应条件下模拟水解反应期间 3'-SLN 和游离唾液酸浓度的变化。反应机理分析表明，相对的初始转唾液酸化速率与水解速率与初始 LacNAc 浓度成正比，转唾液酸化与水解速率常数之比等于 111 M ^–1. 基于与 CGMP 结合的 α-2,3-唾液酸，获得的最大 3'-SLN 产率为 75%。还在酶膜反应器中研究了 CGMP 的分离和酶的再利用。

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Bioactives from Whey: A Sustainable Approach to Enzymatic Production of Sialyl-N-acetyllactosamine

The use of dairy whey to manufacture pharmaceutical products fosters sustainable environmental and economic development. This study represents a new strategy for upgrading of whey to 3′-sialyl-N-acetyllactosamine (3′-SLN) as an important structural component of glycoproteins and a receptor analog capable of forming complexes with hemagglutinins on influenza viruses. N-Acetyllactosamine (LacNAc) was enzymatically produced and purified directly from whey with no pretreatment required. An engineered and recombinantly produced sialidase with trans-sialylation ability from the non-pathogenic Trypanosoma rangeli was then used to transfer sialic acid from whey-derived, sialylated casein glycomacropeptide (CGMP) to this LacNAc. A maximum of 0.92 mM 3′-SLN was obtained at an equimolar ratio of LacNAc to bound sialic acid in CGMP; on the other hand, a molar ratio of 10 gave a fourfold greater 3′-SLN concentration. The variations in the concentration of 3′-SLN and free sialic acid during the hydrolysis reaction were modeled under different reaction conditions using machine learning and mechanistic approaches. The mechanistic analysis of the reaction indicated that the relative initial trans-sialylation rate to hydrolysis rate is directly proportional to the initial LacNAc concentration, with the ratio of trans-sialylation to hydrolysis rate constants equal to 111 M^–1. The maximum 3′-SLN yield obtained was 75% based on α-2,3-sialic acid bound to CGMP. Separation of CGMP and reuse of enzyme were also investigated in an enzymatic membrane reactor.

更新日期：2022-04-08

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