Belitsky Boris R
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA
J Bacteriol. 2015 Apr;197(8):1330-8. doi: 10.1128/JB.02563-14. Epub 2015 Feb 2.
CodY is a branched-chain amino acid-responsive transcriptional regulator that controls the expression of several dozen transcription units in Bacillus subtilis. The presence of isoleucine, valine, and leucine in the growth medium is essential for achieving high activity of CodY and for efficient regulation of the target genes. We identified three permeases-BcaP, BraB, and BrnQ-that are responsible for the bulk of isoleucine and valine uptake and are also involved in leucine uptake. At least one more permease is capable of efficient leucine uptake, as well as low-affinity transport of isoleucine and valine. The lack of the first three permeases strongly reduced activity of CodY in an amino acid-containing growth medium. BcaP appears to be the most efficient isoleucine and valine permease responsible for their utilization as nitrogen sources. The previously described strong CodY-mediated repression of BcaP provides a mechanism for fine-tuning CodY activity by reducing the availability of amino acids and for delaying the utilization of isoleucine and valine as nitrogen and carbon sources under conditions of nutrient excess.
Bacillus subtilis CodY is a global transcriptional regulator that is activated by branched-chain amino acids (BCAA). Since the level of BCAA achieved by intracellular synthesis is insufficient to fully activate CodY, transport of BCAA from the environment is critical for CodY activation, but the permeases needed for such activation have not been previously identified. This study identifies three such permeases, reports their amino acid transport specificity, and reveals their impact on CodY activation.
CodY是一种支链氨基酸响应型转录调节因子，可控制枯草芽孢杆菌中几十个转录单元的表达。生长培养基中异亮氨酸、缬氨酸和亮氨酸的存在对于实现CodY的高活性以及有效调节靶基因至关重要。我们鉴定出三种通透酶——BcaP、BraB和BrnQ——它们负责大部分异亮氨酸和缬氨酸的摄取，也参与亮氨酸的摄取。至少还有一种通透酶能够高效摄取亮氨酸，以及对异亮氨酸和缬氨酸进行低亲和力转运。在前三种通透酶缺失的情况下，含氨基酸的生长培养基中CodY的活性会大幅降低。BcaP似乎是最有效的异亮氨酸和缬氨酸通透酶，负责将它们用作氮源。先前描述的由CodY介导的对BcaP的强烈抑制提供了一种机制，可通过减少氨基酸的可用性来微调CodY的活性，并在营养过剩的条件下延迟将异亮氨酸和缬氨酸用作氮源和碳源。
枯草芽孢杆菌CodY是一种由支链氨基酸（BCAA）激活的全局转录调节因子。由于通过细胞内合成达到的BCAA水平不足以完全激活CodY，因此从环境中转运BCAA对于CodY的激活至关重要，但此前尚未鉴定出这种激活所需的通透酶。本研究鉴定出三种这样的通透酶，报告了它们的氨基酸转运特异性，并揭示了它们对CodY激活的影响。
