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 acetyltransferase. 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.
结论:结核分枝杆菌(Mycobacterium tuberculosis)产生复杂的增强毒力的脂质,其支架由苯并噻唑醇和苯并噻二酮二肉链酸酯(PDIMs)组成。序列分析表明,PDIM合成基因簇中的所谓的聚酮关联蛋白(Pap)编码的PapA5,以及在结核分枝杆菌和其他物种中发现的PapA5同源物,是酰转移酶亚科。重组蛋白的研究证实了PapA5是乙酰转移酶。在结核分枝杆菌中的删除分析表明,papA5对PDIM合成是必需的。我们认为PapA5催化苯并噻唑醇和苯并噻二酮二肉链酸酯与肉链酸酯的二酯化反应。这些研究提供了Pap的功能特性,并允许推断其他Pap在合成复杂脂质,包括抗生素利福霉素中的作用。