Liu Xin-Xin, Shen Meng-Jia, Liu Wei-Bing, Ye Bang-Ce
Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Meilong Rd. 130, Shanghai 200237, China.
School of Chemistry and Chemical Engineering, Shihezi University, Xinjiang, China.
FEMS Microbiol Lett. 2018 May 1;365(9). doi: 10.1093/femsle/fny074.
AccD6 is an important component of acetyl-CoA/propionyl-CoA carboxylase, which acts as a key role in mycolic acid synthesis and short chain fatty acyl-coenzyme A metabolism. In this study, we demonstrated that AccD6 of Mycobacterium smegmatis associates with AccA3 (α subunit of acetyl-CoA carboxylase, MSMEG_1807) and AccE (ε subunit, MSMEG_1812) to form the acetyl-CoA (propionyl-CoA) carboxylase. Results showed that the MSMEG_4331 subunit is a regulator that interacts with the promoter region of accD6 to inhibit its transcription. Transcription of accD6 was reduced by 50% in the mutant M. smegmatis strain overexpressing MSMEG_4331. Moreover, the activity of AccD6 was inhibited by acylation (such as acetylation and propionylation). These results demonstrate that AccD6 of M. smegmatis is regulated at both the transcriptional and post-translational levels. Our findings highlight the novel regulatory mechanism underlying mycolic acid biosynthesis in mycobacteria.
AccD6是乙酰辅酶A/丙酰辅酶A羧化酶的重要组成部分，在分枝菌酸合成和短链脂肪酰辅酶A代谢中起关键作用。在本研究中，我们证明耻垢分枝杆菌的AccD6与AccA3（乙酰辅酶A羧化酶的α亚基，MSMEG_1807）和AccE（ε亚基，MSMEG_1812）结合形成乙酰辅酶A（丙酰辅酶A）羧化酶。结果表明，MSMEG_4331亚基是一种调节因子，它与accD6的启动子区域相互作用以抑制其转录。在过表达MSMEG_4331的耻垢分枝杆菌突变株中，accD6的转录减少了50%。此外，AccD6的活性受到酰化作用（如乙酰化和丙酰化）的抑制。这些结果表明，耻垢分枝杆菌的AccD6在转录和翻译后水平均受到调控。我们的发现突出了分枝杆菌中分枝菌酸生物合成的新调控机制。
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