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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms
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A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms

机译：聚酮化合物合酶催化分枝杆菌和相关生物中分支酸的生物合成的最后缩合步骤

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摘要

Mycolic acids are major and specific constituents of the cell envelope of Corynebacterineae, a suborder of bacterial species including several important human pathogens such as Mycobacterium tuberculosis, Mycobacterium leprae, or Corynebacterium diphthe-riae. These long-chain fatty acids are involved in the unusual architecture and impermeability of the cell envelope of these bacteria. The condensase, the enzyme responsible for the final condensation step in mycolic acid biosynthesis, has remained an enigma for decades. By in silico analysis of various mycobacterial genomes, we identified a candidate enzyme, Pks13, that contains the four catalytic domains required for the condensation reaction. Orthologs of this enzyme were found in other Corynebacterineae species. A Corynebacterium glutamicum strain with a deletion in the pks13 gene was shown to be deficient in mycolic acid production whereas it was able to produce the fatty acids precursors. This mutant strain displayed an altered cell envelope structure. We showed that the pks13 gene was essential for the survival of Mycobacterium smegmatis. A conditional M. smegmatis mutant carrying its only copy of pks13 on a thermosensitive plasmid exhibited mycolic acid biosynthesis defect if grown at nonpermis-sive temperature. These results indicate that Pks13 is the condensase, a promising target for the development of new antimicrobial drugs against Corynebacterineae.
机译：分支杆菌酸是棒状杆菌科（Corynebacterineae）细胞包膜的主要和特定成分，棒状杆菌科是细菌物种的一个亚类，包括几种重要的人类病原体，例如结核分枝杆菌，麻风分枝杆菌或白喉棒状杆菌。这些长链脂肪酸与这些细菌的细胞包膜的异常结构和不渗透性有关。缩合酶是负责霉菌酸生物合成中最后缩合步骤的酶，几十年来一直是一个谜。通过计算机分析各种分枝杆菌基因组，我们确定了一种候选酶Pks13，该酶包含缩合反应所需的四个催化域。该酶的直系同源物在其他棒杆菌属中也发现。 PKS13基因缺失的谷氨酸棒杆菌菌株显示出霉菌酸生产不足，而能够生产脂肪酸前体。该突变株显示出改变的细胞包膜结构。我们表明，pks13基因对于耻垢分枝杆菌的生存至关重要。如果在非渗透温度下生长，则在热敏质粒上仅携带pks13拷贝的条件性耻垢分枝杆菌突变体表现出霉菌酸生物合成缺陷。这些结果表明，Pks13是缩合酶，这是开发针对棒杆菌的新型抗菌药物的有希望的目标。

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