Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
J Bacteriol. 2018 Jun 11;200(13). doi: 10.1128/JB.00685-17. Print 2018 Jul 1.
The GntR family regulator DasR controls the transcription of genes involved in chitin and -acetylglucosamine (GlcNAc) metabolism in actinobacteria. GlcNAc is catabolized to ammonia, fructose-6-phosphate (Fru-6P), and acetate, which are nitrogen and carbon sources. In this work, a DasR-responsive element () was observed in the upstream region of in This gene encodes acetyl coenzyme A (acetyl-CoA) synthetase (Acs), an enzyme that catalyzes the conversion of acetate into acetyl-CoA. We found that DasR repressed the transcription of in response to carbon availability, especially with GlcNAc. Growth inhibition was observed in a -deleted mutant (Δ) in the presence of GlcNAc in minimal medium containing 10 mM acetate, a condition under which Acs activity is critical to growth. These results demonstrate that DasR controls acetate assimilation by directly repressing the transcription of the gene and performs regulatory roles in the production of intracellular acetyl-CoA in response to GlcNAc. Our work has identified the DasR GlcNAc-sensing regulator that represses the generation of acetyl-CoA by controlling the expression of acetyl-CoA synthetase, an enzyme responsible for acetate assimilation in The finding provides the first insights into the importance of DasR in the regulation of acetate metabolism, which encompasses the regulatory network between nitrogen and carbon metabolism in actinobacteria, in response to environmental changes.
GntR 家族调控因子 DasR 控制着放线菌中参与几丁质和 N-乙酰葡萄糖胺 (GlcNAc) 代谢的基因的转录。GlcNAc 被分解为氨、果糖-6-磷酸 (Fru-6P) 和乙酸，它们是氮源和碳源。在这项工作中，我们在 的上游区域观察到了一个 DasR 响应元件 ()。该基因编码乙酰辅酶 A (acetyl-CoA) 合成酶 (Acs)，该酶催化乙酸转化为乙酰-CoA。我们发现，DasR 响应碳源可用性，特别是 GlcNAc，抑制了 的转录。在含有 10mM 乙酸的最小培养基中，当 GlcNAc 存在时，Δ 缺失突变体 (Δ) 的生长受到抑制，在这种条件下，Acs 活性对生长至关重要。这些结果表明，DasR 通过直接抑制 基因的转录来控制乙酸同化，并在响应 GlcNAc 时在细胞内乙酰-CoA 的产生中发挥调节作用。我们的工作确定了 DasR 作为 GlcNAc 感应调控因子，通过控制负责乙酸同化的乙酰辅酶 A 合成酶的表达来抑制乙酰-CoA 的产生。这一发现首次揭示了 DasR 在响应环境变化时，对放线菌中氮碳代谢之间的调节网络中乙酸代谢的调节的重要性。
