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利用糖苷酶生产人参皂苷的生物催化策略:现状与展望。

Biocatalytic strategies for the production of ginsenosides using glycosidase: current state and perspectives.

机构信息

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, 710069, Shaanxi, China.

Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, 710069, Shaanxi, China.

出版信息

Appl Microbiol Biotechnol. 2020 May;104(9):3807-3823. doi: 10.1007/s00253-020-10455-9. Epub 2020 Mar 3.

Abstract

Panax ginseng is a traditional Chinese medicine with significant pharmaceutical effects and broad application. Rare ginsenosides with high antitumor activities can be generated via oriented modification of their glycosyl moiety. For this purpose, suitable microorganisms and their enzymatic systems can be used. In this review, we address several issues associated with these systems. Under aerobic conditions, fungus biotransformation provides an efficient and inexpensive biotransformation process that can be easily scaled up. Considering the profound use of probiotics, wild strains generally recognized as safe have shown a potential through classical fermentation in food manufacturers of deglycosylated ginsenosides. Commonly applied recombinant enzymes from E. coli, especially recombinant hyperthermophilic enzymes, showed efficient conversion in biomedical or pharmaceutical industries. In this review, key genes dedicated to the production of ginsenosides (especially in Saccharomyces cerevisiae) are highlighted in relation to the large-scale production of ginsenosides. We also evaluate biocatalytic strategies that are aimed to improve product specificity and biocatalytic efficiency with industrial applications. Perspectives of protein engineering and solvent engineering in the development and large-scale preparation of ginsenosides in anticancer drugs, food and health care products are explored. KEY POINTS : • Modification of ginsenosides with food/engineered microorganisms is summarized. • Optimization of cell factories by protein engineering remains challenging. • Solvent engineering offers an attractive potential alternative.

摘要

人参是一种具有重要药用价值和广泛应用的中药。通过对其糖基部分进行定向修饰,可以产生具有高抗肿瘤活性的稀有皂苷。为此,可以利用合适的微生物及其酶系统。在这篇综述中,我们讨论了与这些系统相关的几个问题。在有氧条件下,真菌生物转化提供了一种高效、廉价的生物转化过程,易于放大。考虑到益生菌的广泛应用,通常被认为是安全的野生菌株通过食品制造商的经典发酵,已经显示出了具有潜力的去糖基化人参皂苷。来自大肠杆菌的常用重组酶,特别是重组嗜热酶,在生物医学或制药行业表现出了高效的转化。在这篇综述中,与大规模生产人参皂苷相关,重点介绍了专门用于生产人参皂苷的关键基因(特别是在酿酒酵母中)。我们还评估了旨在提高产品特异性和生物催化效率的生物催化策略及其工业应用。探讨了蛋白质工程和溶剂工程在抗癌药物、食品和保健品中人参皂苷的开发和大规模制备中的应用前景。关键点:• 总结了用人或工程微生物修饰人参皂苷的方法。• 通过蛋白质工程优化细胞工厂仍然具有挑战性。• 溶剂工程提供了有吸引力的替代方案。

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