發(fā)布時(shí)間：2018-11-17 10:19

【摘要】：蛋白質(zhì)賴氨酸�；�化是一種廣泛存在于生物體內(nèi),調(diào)控多種細(xì)胞生理過(guò)程的重要機(jī)制。生物體內(nèi)存在兩種酰基化修飾方式:基于�；�轉(zhuǎn)移酶的酰基化反應(yīng)和非酶催化�；�化反應(yīng)。現(xiàn)有研究表明,蛋白質(zhì)賴氨酸�；�化在響應(yīng)營(yíng)養(yǎng)物代謝、調(diào)節(jié)蛋白質(zhì)功能和影響代謝酶活性方面起著重要作用。為了了解兩種蛋白質(zhì)�；�化修飾方式的差異及其對(duì)乙酸及丙酸代謝的影響,本文做了以下兩個(gè)方面的工作:(1)乙酸代謝及兩種�；�化(非酶催化和酶催化)修飾的比較研究。乙酰輔酶A合成酶(Acetyl-CoAsynthase,AcsA,EC:6.2.1.1)是乙酸代謝的關(guān)鍵酶,研究顯示AcsA的活性受到�；�化修飾的調(diào)控。本文對(duì)調(diào)控AcsA的兩種酰基化修飾進(jìn)行研究,描述了調(diào)控AcsA功能的翻譯后修飾系統(tǒng),發(fā)現(xiàn)了�；�化修飾具有時(shí)間和濃度依賴性,闡述了酰基化位點(diǎn)的動(dòng)態(tài)變化和優(yōu)先性,揭示了兩種�；�化修飾方式的差異,拓展了我們對(duì)酰基化修飾機(jī)制的認(rèn)識(shí),為后續(xù)基于�；�化修飾修飾層面對(duì)菌種改造提供了新的干預(yù)節(jié)點(diǎn)。(2)糖多孢紅霉菌丙酰CoA合成酶�；�化對(duì)紅霉素產(chǎn)量的影響。丙酰輔酶A(Propionyl-Coenzyme A,Pr-CoA)是酰基化的供體,也是糖多孢紅霉菌紅霉素合成的前體,本文從響應(yīng)丙酸誘導(dǎo)的關(guān)鍵酶丙酰CoA合成酶(Propionyl-CoA synthase,PrpE,EC:6.2.1.17)的轉(zhuǎn)錄水平和翻譯后修飾層面進(jìn)行研究,發(fā)現(xiàn)糖多孢紅霉菌中的丙�；�修飾對(duì)PrpE具有調(diào)控作用,并通過(guò)�；�化層面在菌體內(nèi)過(guò)表達(dá)SACE_1780,提高了糖多孢紅霉菌的紅霉素產(chǎn)量至140%。該研究不僅完善了放線菌蛋白質(zhì)酰基化研究,還建立了一種通過(guò)�；�化修飾干預(yù)紅霉素合成的策略。
[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.
【學(xué)位授予單位】：華東理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：TQ225.12;Q78

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