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结核分枝杆菌中的β-酮酰基-ACP 合酶作为潜在的药物靶点。

The β-ketoacyl-ACP synthase from Mycobacterium tuberculosis as potential drug targets.

机构信息

Epigenomics Project, Institute of Systems and Synthetic Biology, Universite d'Evry Val d'Essonne-Genopole-CNRS UPS3201, 5 rue Henri Desbrueres, 91030 Evry, France.

出版信息

Curr Med Chem. 2011;18(9):1318-24. doi: 10.2174/092986711795029636.

Abstract

The continuous preventive measures and control of tuberculosis are often hampered by re-emergence of multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis. A novel drug approach is desperately needed to combat the global threat posed by MDR strains. In spite of current advancement in biological techniques viz. microarray and proteomics data for tuberculosis, no such potent drug has been developed in the past decades yet. Therefore, mycolic acid is an essential constituent which is involved in the formation of cell wall of Mycobacterium species. The biosynthesis of mycolic acid is involved in two fatty acid synthase systems, the multifunctional polypeptide fatty acid synthase I (FASI) which performs de novo fatty acid synthesis and dissociate FASII system. FASII system consists of monofunctional enzymes and acyl carrier protein (ACP), elongating FASI products to long chain mycolic acid precursor. In this review, the β-ketoacyl-ACP synthases (fadH, kasA and kasB) are distinct and play a vital role in mycolic acid synthesis, cell wall synthesis, biofilm formation and also pathogenesis. On the basis of substantial observation we suggest that these enzymes may be used as promising and attractive targets for novel anti-TB drugs designing and discovery.

摘要

结核分枝杆菌(Mycobacterium tuberculosis)耐多药(MDR)菌株的再次出现,常常会阻碍结核病的持续预防措施和控制。急需一种新的药物方法来应对耐多药菌株所构成的全球威胁。尽管目前在生物技术方面取得了进展,例如结核分枝杆菌的微阵列和蛋白质组学数据,但在过去几十年中尚未开发出这种有效的药物。因此,分枝菌酸是一种重要的成分,参与分枝杆菌属细胞的形成。分枝菌酸的生物合成涉及两种脂肪酸合酶系统,多功能多肽脂肪酸合酶 I(FASI)进行从头脂肪酸合成和分离 FASII 系统。FASII 系统由单功能酶和酰基载体蛋白(ACP)组成,将 FASI 产物延伸为长链分枝菌酸前体。在这篇综述中,β-酮酰-ACP 合酶( fadH、kasA 和 kasB)是不同的,在分枝菌酸合成、细胞壁合成、生物膜形成以及发病机制中起着至关重要的作用。基于大量的观察,我们认为这些酶可以作为新型抗结核药物设计和发现的有希望和有吸引力的靶点。

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