THE BIOSYNTHESIS OF CYCLOPROPANATED MYCOLIC ACIDS IN MYCOBACTERIUM-TUBERCULOSIS - IDENTIFICATION AND FUNCTIONAL-ANALYSIS OF CMAS-2
THE BIOSYNTHESIS OF CYCLOPROPANATED MYCOLIC ACIDS IN MYCOBACTERIUM-TUBERCULOSIS - IDENTIFICATION AND FUNCTIONAL-ANALYSIS OF CMAS-2
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DOI：
10.1074/jbc.270.45.27292
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发表时间：
1995-11-10
影响因子：
4.8
通讯作者：
BARRY, CE
中科院分区：
文献类型：
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作者：
GEORGE, KM;YUAN, Y;BARRY, CE
结核分枝杆菌产生的主要分枝菌酸在部分分枝菌酸链中含有两个顺式环丙烷。其产物环丙烷化近端双键的基因通过与麻风分枝杆菌基因组测序计划中鉴定的推定环丙烷合酶同源而克隆。该基因命名为cma 2，经测序发现与cma 1（使远端双键环丙烷化）有52%的同一性，与M.麻风病人发现这两种cma基因在分枝杆菌的致病性物种中分布受限。在耻垢分枝杆菌中cma 2的表达导致α（1）系列分枝菌酸中近端双键的环丙烷化。两种环丙烷脱氢酶的共表达导致两个中心的环丙烷化，产生结构上类似于结核分枝杆菌α-二环丙基分枝杆菌的分子。纯化的细胞壁和分枝菌酸的差示扫描量热法表明，近端位置的环丙烷化使观察到的转变温度提高了3 ℃。这些结果表明，环丙烷化有助于细胞壁复合物的结构完整性。
The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. The gene whose product cyclopropanates the proximal double bond was cloned by homology to a putative cyclopropane synthase identified from the Mycobacterium leprae genome sequencing project. This gene, named cma2, was sequenced and found to be 52% identical to cma1 (which cyclopropanates the distal double bond) and 73% identical to the gene from M. leprae. Both cma genes were found to be restricted in distribution to pathogenic species of mycobacteria. Expression of cma2 in Mycobacterium smegmatis resulted in the cyclopropanation of the proximal double bond in the alpha(1), series of mycolic acids. Coexpression of both cyclopropane synthases resulted in cyclopropanation of both centers, producing a molecule structurally similar to the M; tuberculosis alpha-dicyclopropyl mycolates. Differential scanning calorimetry of purified cell walls and mycolic acids demonstrated that cyclopropanation of the proximal position raised the observed transition temperature by 3 degrees C. These results suggest that cyclepropanation contributes to the structural integrity of the cell wall complex.