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Flavonoids, terpenoids, and polyketide antibiotics: Role of glycosylation and biocatalytic tactics in engineering glycosylation.
Biotechnology Advances ( IF 16.0 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.biotechadv.2020.107550
Ushasree Mrudulakumari Vasudevan 1 , Eun Yeol Lee 1
Affiliation  

Flavonoids, terpenoids, and polyketides are structurally diverse secondary metabolites used widely as pharmaceuticals and nutraceuticals. Most of these molecules exist in nature as glycosides, in which sugar residues act as a decisive factor in their architectural complexity and bioactivity. Engineering glycosylation through selective trimming or extension of the sugar residues in these molecules is a prerequisite to their commercial production as well to creating novel derivatives with specialized functions. Traditional chemical glycosylation methods are tedious and can offer only limited end-product diversity. New in vitro and in vivo biocatalytic tools have emerged as outstanding platforms for engineering glycosylation in these three classes of secondary metabolites to create a large repertoire of versatile glycoprofiles. As knowledge has increased about secondary metabolite–associated promiscuous glycosyltransferases and sugar biosynthetic machinery, along with phenomenal progress in combinatorial biosynthesis, reliable industrial production of unnatural secondary metabolites has gained momentum in recent years. This review highlights the significant role of sugar residues in naturally occurring flavonoids, terpenoids, and polyketide antibiotics. General biocatalytic tools used to alter the identity and pattern of sugar molecules are described, followed by a detailed illustration of diverse strategies used in the past decade to engineer glycosylation of these valuable metabolites, exemplified with commercialized products and patents. By addressing the challenges involved in current bio catalytic methods and considering the perspectives portrayed in this review, exceptional drugs, flavors, and aromas from these small molecules could come to dominate the natural-product industry.



中文翻译:

类黄酮,萜类化合物和聚酮化合物抗生素:糖基化和生物催化策略在糖基化工程中的作用。

类黄酮,萜类化合物和聚酮化合物是结构多样的次生代谢产物,广泛用作药物和营养保健品。这些分子中的大多数在自然界中以糖苷形式存在,其中糖残基在其结构复杂性和生物活性中起决定性作用。通过选择性修剪或延伸这些分子中的糖残基来工程化糖基化是其商业生产以及产生具有特殊功能的新型衍生物的先决条件。传统的化学糖基化方法很繁琐,只能提供有限的最终产品多样性。新体外体内生物催化工具已经成为在这三类次生代谢物中工程化糖基化的杰出平台,以创造出多种多样的通用糖谱。随着对次生代谢物相关的混杂糖基转移酶和糖生物合成机制的了解增加,以及组合生物合成的显着进展,近年来,非天然次生代谢物的可靠工业生产得到了发展。这篇评论强调了糖残基在天然类黄酮,类萜和聚酮化合物抗生素中的重要作用。描述了用于改变糖分子身份和模式的一般生物催化工具,其次是过去十年中用于工程化这些有价值的代谢产物糖基化的多种策略的详细说明,以商业化产品和专利为例。通过解决当前生物催化方法所面临的挑战并考虑本综述所描述的观点,这些小分子的优异药物,风味和香气可能会主导天然产品行业。

更新日期:2020-05-01
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