分枝杆菌聚酮化合物相关蛋白是酰基转移酶：以结核分枝杆菌PapA5为例的原理证明
Mycobacterial polyketide-associated proteins are acyltransferases: proof of principle with Mycobacterium tuberculosis PapA5.
作者信息
Onwueme Kenolisa C, Ferreras Julian A, Buglino John, Lima Christopher D, Quadri Luis E N
机构信息
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
出版信息
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4608-13. doi: 10.1073/pnas.0306928101. Epub 2004 Mar 18.
Abstract
Mycobacterium tuberculosis (Mt) produces complex virulence-enhancing lipids with scaffolds consisting of phthiocerol and phthiodiolone dimycocerosate esters (PDIMs). Sequence analysis suggested that PapA5, a so-called polyketide-associated protein (Pap) encoded in the PDIM synthesis gene cluster, as well as PapA5 homologs found in Mt and other species, are a subfamily of acyltransferases. Studies with recombinant protein confirmed that PapA5 is an acyltransferase [corrected]. Deletion analysis in Mt demonstrated that papA5 is required for PDIM synthesis. We propose that PapA5 catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosate. These studies present the functional characterization of a Pap and permit inferences regarding roles of other Paps in the synthesis of complex lipids, including the antibiotic rifamycin.
摘要
结核分枝杆菌（Mt）产生具有复杂毒力增强脂质，其支架由结核硬脂醇和结核双分枝菌酸酯（PDIMs）组成。序列分析表明，PapA5是一种在PDIM合成基因簇中编码的所谓聚酮化合物相关蛋白（Pap），以及在Mt和其他物种中发现的PapA5同源物，是酰基转移酶的一个亚家族。重组蛋白研究证实PapA5是一种酰基转移酶[已修正]。Mt中的缺失分析表明，papA5是PDIM合成所必需的。我们提出，PapA5催化结核硬脂醇和结核双分枝菌酸与分枝菌酸的二酯化反应。这些研究展示了一种Pap的功能特性，并允许推断其他Paps在包括抗生素利福霉素在内的复杂脂质合成中的作用。
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