关键词: Saccharomyces cerevisiae Uridine diphosphate sugar metabolism glycosides glycosylation natural products nucleotide sugar

Mesh : Saccharomyces cerevisiae / metabolism genetics Glycosylation Metabolic Engineering / methods Biological Products / metabolism Nucleotides / metabolism Metabolic Networks and Pathways

来  源:   DOI:10.1021/acssynbio.3c00737   PDF(Pubmed)

Abstract:
Glycosylation is a ubiquitous modification present across all of biology, affecting many things such as physicochemical properties, cellular recognition, subcellular localization, and immunogenicity. Nucleotide sugars are important precursors needed to study glycosylation and produce glycosylated products. Saccharomyces cerevisiae is a potentially powerful platform for producing glycosylated biomolecules, but it lacks nucleotide sugar diversity. Nucleotide sugar metabolism is complex, and understanding how to engineer it will be necessary to both access and study heterologous glycosylations found across biology. This review overviews the potential challenges with engineering nucleotide sugar metabolism in yeast from the salvage pathways that convert free sugars to their associated UDP-sugars to de novo synthesis where nucleotide sugars are interconverted through a complex metabolic network with governing feedback mechanisms. Finally, recent examples of engineering complex glycosylation of small molecules in S. cerevisiae are explored and assessed.
摘要:
糖基化是一种普遍存在于所有生物学中的修饰,影响许多东西,如物理化学性质,细胞识别,亚细胞定位,和免疫原性。核苷酸糖是研究糖基化和产生糖基化产物所需的重要前体。酿酒酵母是生产糖基化生物分子的潜在强大平台,但它缺乏核苷酸糖的多样性。核苷酸糖代谢是复杂的,并了解如何设计它将有必要获得和研究跨生物学发现的异源糖基化。这篇综述概述了酵母中核苷酸糖代谢工程的潜在挑战,从将游离糖转化为其相关的UDP糖的补救途径到从头合成,其中核苷酸糖通过具有控制反馈机制的复杂代谢网络相互转化。最后,探索和评估了酿酒酵母中小分子的工程复杂糖基化的最新实例。
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