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通向α-酮戊二酸的生化途径,一种多面性的代谢物。

Biochemical pathways to α-ketoglutarate, a multi-faceted metabolite.

作者信息

Legendre F, MacLean A, Appanna V P, Appanna V D

机构信息

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada.

出版信息

World J Microbiol Biotechnol. 2020 Jul 20;36(8):123. doi: 10.1007/s11274-020-02900-8.

DOI:10.1007/s11274-020-02900-8
PMID:32686016
Abstract

α-Ketoglutarate (AKG) also known as 2-oxoglutarate is an essential metabolite in virtually all organisms as it participates in a variety of biological processes including anti-oxidative defence, energy production, signalling modules, and genetic modification. This keto-acid also possesses immense commercial value as it is utilized as a nutritional supplement, a therapeutic agent, and a precursor to a variety of value-added products such as ethylene and heterocyclic compounds. Hence, the generation of KG in a sustainable and environmentally-neutral manner is a major ongoing research endeavour. In this mini-review, the enzymatic systems and the metabolic networks mediating the synthesis of AKG will be described. The importance of such enzymes as isocitrate dehydrogenase (ICDH), glutamate dehydrogenase (GDH), succinate semialdehyde dehydrogenase (SSADH) and transaminases that directly contribute to the formation of KG will be emphasized. The efficacy of microbial systems in providing an effective platform to generate this moiety and the molecular strategies involving genetic manipulation, abiotic stress and nutrient supplementation that result in the optimal production of AKG will be evaluated. Microbial systems and their components acting via the metabolic networks and the resident enzymes are well poised to provide effective biotechnological tools that can supply renewable AKG globally.

摘要

α-酮戊二酸(AKG)也称为2-氧代戊二酸,是几乎所有生物体中的一种必需代谢物,因为它参与多种生物过程,包括抗氧化防御、能量产生、信号传导模块和基因修饰。这种酮酸还具有巨大的商业价值,因为它被用作营养补充剂、治疗剂以及多种增值产品(如乙烯和杂环化合物)的前体。因此,以可持续且环境中性的方式生成α-酮戊二酸是当前一项主要的研究工作。在本综述中,将描述介导α-酮戊二酸合成的酶系统和代谢网络。将强调异柠檬酸脱氢酶(ICDH)、谷氨酸脱氢酶(GDH)、琥珀酸半醛脱氢酶(SSADH)和转氨酶等直接参与α-酮戊二酸形成的酶的重要性。将评估微生物系统在提供有效平台以生成该部分物质方面的功效,以及涉及基因操作、非生物胁迫和营养补充的分子策略,这些策略可实现α-酮戊二酸的最佳产量。微生物系统及其通过代谢网络和固有酶发挥作用的组件,有望提供有效的生物技术工具,从而在全球范围内供应可再生的α-酮戊二酸。

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