The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis.
The mycobacterial desaturase DesA2 is associated with mycolic acid biosynthesis.
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DOI：
10.1038/s41598-022-10589-y
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发表时间：
2022-04-28
影响因子：
4.6
通讯作者：
Bhatt, Apoorva
中科院分区：
文献类型：
--
作者：
Bailo, Rebeca;Radhakrishnan, Anjana;Singh, Albel;Nakaya, Makoto;Fujiwara, Nagatoshi;Bhatt, Apoorva
霉菌酸对结核分枝杆菌（结核的病原体）的生存和毒力至关重要。尽管我们之前已经证明编码需氧去饱和酶的desA1参与了霉菌酸的去饱和，但对霉菌酸的巯基链中双键的形成仍然知之甚少。在这里，我们发现由desA2编码的第二种去饱和酶也参与真菌酸的生物合成。DesA2是实验室培养基中快速生长的耻垢分枝杆菌生长所必需的。DesA2的条件耗尽导致霉菌酸生物合成的减少和分枝杆菌活力的丧失。此外，desa2缺失的细胞还积累了链长为C19-C24的脂肪酸。DesA2耗尽后霉菌酸生物合成完全丧失，并且缺乏任何单烯衍生物（发现在DesA1耗尽时积累），这表明DesA2在霉菌酸生物合成机制中的早期作用，突出了其作为药物靶点的潜力。
Mycolic acids are critical for the survival and virulence of Mycobacterium tuberculosis, the causative agent of tuberculosis. Double bond formation in the merochain of mycolic acids remains poorly understood, though we have previously shown desA1, encoding an aerobic desaturase, is involved in mycolic acid desaturation. Here we show that a second desaturase encoded by desA2 is also involved in mycolate biosynthesis. DesA2 is essential for growth of the fast-growing Mycobacterium smegmatis in laboratory media. Conditional depletion of DesA2 led to a decrease in mycolic acid biosynthesis and loss of mycobacterial viability. Additionally, DesA2-depleted cells also accumulated fatty acids of chain lengths C19-C24. The complete loss of mycolate biosynthesis following DesA2 depletion, and the absence of any monoenoic derivatives (found to accumulate on depletion of DesA1) suggests an early role for DesA2 in the mycolic acid biosynthesis machinery, highlighting its potential as a drug target.
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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
影响因子：
6.4
作者：
DeJesus MA;Gerrick ER;Xu W;Park SW;Long JE;Boutte CC;Rubin EJ;Schnappinger D;Ehrt S;Fortune SM;Sassetti CM;Ioerger TR
通讯作者：
Ioerger TR
影响因子：
3.2
作者：
Vilchèze, C;Morbidoni, HR;Jacobs, WR
通讯作者：
Jacobs, WR
影响因子：
3.2
作者：
Bhatt, A;Kremer, L;Jacobs, WR
通讯作者：
Jacobs, WR
影响因子：
11.3
作者：
Gago G;Diacovich L;Arabolaza A;Tsai SC;Gramajo H
通讯作者：
Gramajo H