蛋白质酰基化修饰对乙酸及丙酸代谢的影响

发布时间：2018-11-17 10:19

【摘要】：蛋白质赖氨酸酰基化是一种广泛存在于生物体内,调控多种细胞生理过程的重要机制。生物体内存在两种酰基化修饰方式:基于酰基转移酶的酰基化反应和非酶催化酰基化反应。现有研究表明,蛋白质赖氨酸酰基化在响应营养物代谢、调节蛋白质功能和影响代谢酶活性方面起着重要作用。为了了解两种蛋白质酰基化修饰方式的差异及其对乙酸及丙酸代谢的影响,本文做了以下两个方面的工作:(1)乙酸代谢及两种酰基化(非酶催化和酶催化)修饰的比较研究。乙酰辅酶A合成酶(Acetyl-CoAsynthase,AcsA,EC:6.2.1.1)是乙酸代谢的关键酶,研究显示AcsA的活性受到酰基化修饰的调控。本文对调控AcsA的两种酰基化修饰进行研究,描述了调控AcsA功能的翻译后修饰系统,发现了酰基化修饰具有时间和浓度依赖性,阐述了酰基化位点的动态变化和优先性,揭示了两种酰基化修饰方式的差异,拓展了我们对酰基化修饰机制的认识,为后续基于酰基化修饰修饰层面对菌种改造提供了新的干预节点。(2)糖多孢红霉菌丙酰CoA合成酶酰基化对红霉素产量的影响。丙酰辅酶A(Propionyl-Coenzyme A,Pr-CoA)是酰基化的供体,也是糖多孢红霉菌红霉素合成的前体,本文从响应丙酸诱导的关键酶丙酰CoA合成酶(Propionyl-CoA synthase,PrpE,EC:6.2.1.17)的转录水平和翻译后修饰层面进行研究,发现糖多孢红霉菌中的丙酰化修饰对PrpE具有调控作用,并通过酰基化层面在菌体内过表达SACE_1780,提高了糖多孢红霉菌的红霉素产量至140%。该研究不仅完善了放线菌蛋白质酰基化研究,还建立了一种通过酰基化修饰干预红霉素合成的策略。
[Abstract]:Lysine acylation of protein is an important mechanism that widely exists in organisms and regulates various cellular physiological processes. There are two types of acylation modification in vivo: acylation based on acyltransferase and non-enzymatic-catalyzed acylation. Recent studies have shown that protein lysine acylation plays an important role in responding to nutrient metabolism, regulating protein function and affecting metabolic enzyme activity. In order to understand the difference of acylation modification of two proteins and its effect on the metabolism of acetic acid and propionic acid, In this paper, the following two aspects have been done: (1) the comparative study of acetic acid metabolism and two acylation (non-enzymatic catalysis and enzymatic catalysis) modification. Acetyl coenzyme A synthase (Acetyl-CoAsynthase,AcsA,EC:6.2.1.1) is a key enzyme in acetic acid metabolism. It has been shown that the activity of AcsA is regulated by acylation modification. In this paper, two kinds of acylation modifications regulating AcsA were studied, and the posttranslational modification system for regulating the function of AcsA was described. It was found that the acylation modification was time-and concentration-dependent, and the dynamic changes and priorities of acylation sites were described. The differences between two kinds of acylation modification methods are revealed and our understanding of acylation modification mechanism is expanded. It provides a new intervention node for the subsequent modification based on acylation modification. (2) the effect of acylation of glycosylated erythromycete propionyl CoA synthase on the yield of erythromycin. Propionyl-Coenzyme (Propionyl-Coenzyme) Pr-CoA is an acylated donor and precursor of erythromycin synthesis. In this paper, the key enzyme propionyl CoA synthase (Propionyl-CoA synthase,PrpE,) was induced by propionic acid. The transcriptional level and posttranslational modification level of EC:6.2.1.17) were studied. It was found that propionylation modification in glycosporycoryces could regulate PrpE and express SACE_1780, in vivo through acylation level. The Erythromycin yield of Erythromycetes increased to 140%. This study not only improved acylation of actinomycetes protein, but also established a strategy to intervene erythromycin synthesis by acylation modification.
【学位授予单位】：华东理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ225.12;Q78

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