Identification of a Desaturase Involved in Mycolic Acid Biosynthesis in Mycobacterium smegmatis.
Identification of a Desaturase Involved in Mycolic Acid Biosynthesis in Mycobacterium smegmatis.
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DOI：
10.1371/journal.pone.0164253
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Bhatt A
中科院分区：
文献类型：
--
作者：
Singh A;Varela C;Bhatt K;Veerapen N;Lee OY;Wu HH;Besra GS;Minnikin DE;Fujiwara N;Teramoto K;Bhatt A
霉菌酸是一种独特的长链脂肪酸，存在于包括结核杆菌在内的分枝杆菌细胞壁中。霉菌酸中双键的引入仍然知之甚少，然而，编码两种潜在的有氧去饱和酶的基因被认为参与了这一过程。我们发现其中一个基因desA1对腐生耻垢分枝杆菌的生长至关重要。耻毛分枝杆菌条件突变体中desA1的缺失导致霉菌酸生物合成的减少和生存能力的丧失。desa1缺失的细胞表现出另外两种表型：使用14[C]标记，我们检测到在银TLC板上迁移更快的少量霉菌酸相关物种的积累。螺旋飞行时间质谱分析表明，存在与α-霉菌酸单烯衍生物相对应的物种。此外，条件耗尽导致裂解细胞中存在长度为~C26-C48的游离脂肪酰基。在条件突变体中，结核分枝杆菌desA1可以挽救细胞活力，这突出了desA1作为致病性分枝杆菌的新药物靶点的潜力。
Mycolic acids are unique long chain fatty acids found in the cell walls of mycobacteria including the tubercle bacillus, Mycobacterium tuberculosis. The introduction of double bonds in mycolic acids remains poorly understood, however, genes encoding two potential aerobic desaturases have been proposed to be involved in this process. Here we show that one of these genes, desA1, is essential for growth of the saprophytic Mycobacterium smegmatis. Depletion of desA1 in a M. smegmatis conditional mutant led to reduction of mycolic acid biosynthesis and loss of viability. The DesA1-depleted cells exhibited two other phenotypes: using 14[C]-labelling, we detected the accumulation of minor mycolic acid-related species that migrated faster in a silver TLC plate. Spiral Time of Flight Mass Spectroscopic analysis suggested the presence of species with sizes corresponding to what were likely monoenoic derivatives of α-mycolic acids. Additionally, conditional depletion led to the presence of free fatty acyl species of lengths ~C26-C48 in the lysing cells. Cell viability could be rescued in the conditional mutant by Mycobacterium tuberculosis desA1, highlighting the potential of desA1 as a new drug target in pathogenic mycobacteria.
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分枝菌酸：破译并瞄准结核杆菌的致命弱点。
影响因子：
3.6
作者：
Nataraj V;Varela C;Javid A;Singh A;Besra GS;Bhatt A
通讯作者：
Bhatt A
DOI：
10.1111/j.1432-1033.1970.tb00304.x
发表时间：
1970-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
ASSELINE.CP;LACAVE, CS;PROME, JC
通讯作者：
PROME, JC
影响因子：
3.2
作者：
Bhatt, A;Kremer, L;Jacobs, WR
通讯作者：
Jacobs, WR
影响因子：
2.8
作者：
Bardarov, S;Bardarov, S;Jacobs, WR
通讯作者：
Jacobs, WR
影响因子：
3.6
作者：
Bernut, Audrey;Viljoen, Albertus;Kremer, Laurent
通讯作者：
Kremer, Laurent