論文 - 詳細
| RRC ID | 35424 |
|---|---|
| 著者 | Brinsmade SR, Sonenshein AL. |
| タイトル | Dissecting complex metabolic integration provides direct genetic evidence for CodY activation by guanine nucleotides. |
| ジャーナル | J Bacteriol |
| Abstract |
The global regulator CodY controls the expression of dozens of metabolic genes and genes mediating adaptation to nutrient availability in many low-G+C Gram-positive bacteria. Branched-chain amino acids L-isoleucine, L-leucine, and L-valine (ILV) activate CodY both in vivo and in vitro, and genes that direct their synthesis (ilv, ybgE, and ywaA) are highly repressed by CodY, creating a potential negative feedback loop. The nucleoside triphosphate GTP also activates CodY in vitro, but the evidence for activation by GTP in vivo is limited and indirect. We constructed a Bacillus subtilis strain (ybgE bcd ywaA) that is unable to convert branched-chain α-keto acids to ILV or to use ILV as a precursor for branched-chain fatty acid synthesis. Unexpectedly, the strain was not viable on rich medium. Supplementing rich medium with short, branched-chain fatty acids or derepressing expression of genes for de novo ILV synthesis bypassed the original lethality, restoring growth and showing that the lack of viability was due to insufficient intracellular production of the precursors of branched-chain fatty acids. Spontaneous extragenic suppressor mutants that arose in the triple mutant population proved to have additional mutations in guaA or guaB or codY. Expression of ILV biosynthetic genes in codY mutants was increased. The gua mutations caused guanine/guanosine auxotrophy and led to partial derepression of direct CodY-repressed targets, including ILV biosynthetic genes, under conditions similar to those that caused the original lethality. We conclude that a guanine derivative, most likely GTP, controls CodY activity in vivo. |
| 巻・号 | 193(20) |
| ページ | 5637-48 |
| 公開日 | 2011-10-1 |
| DOI | 10.1128/JB.05510-11 |
| PII | JB.05510-11 |
| PMID | 21856856 |
| PMC | PMC3187194 |
| MeSH | Amino Acids, Branched-Chain / metabolism Bacillus subtilis / genetics Bacillus subtilis / metabolism* Bacterial Proteins / genetics* Bacterial Proteins / metabolism Gene Expression Regulation, Bacterial* Guanine Nucleotides / metabolism* Guanosine Triphosphate / metabolism Transcription Factors / genetics* Transcription Factors / metabolism Transcriptional Activation* |
| IF | 3.006 |
| 引用数 | 25 |
| WOS 分野 | MICROBIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 原核生物(枯草菌) | |