Department of Biotechnology, Graduate School of Agriculture and Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Mol Microbiol. 2011 Sep;81(6):1607-22. doi: 10.1111/j.1365-2958.2011.07795.x. Epub 2011 Aug 22.
AdpA is a global transcriptional regulator that is induced by the microbial hormone A-factor and activates many genes required for morphological differentiation and secondary metabolism in Streptomyces griseus. We confirmed that the regulatory tRNA gene bldA was required for translation of TTA-containing adpA. We also demonstrated that AdpA bound two sites upstream of the bldA promoter and activated transcription of bldA. Thus, we revealed a unique positive feedback loop between AdpA and BldA in S. griseus. Forced expression of bldA in an A-factor-deficient mutant resulted in the partial restoration of aerial mycelium formation and streptomycin production, suggesting that the positive feedback loop could prevent premature transcriptional activation of the AdpA-target genes in the wild-type strain. We revealed that the morphological defect of the bldA mutant could be attributed mainly to the TTA codons of only two genes: adpA and amfR. amfR encodes a transcriptional activator essential for aerial mycelium formation and is a member of the AdpA regulon. Thus, amfR is regulated by a feedforward mechanism involving AdpA and BldA. We concluded that the central regulatory unit composed of AdpA and BldA plays important roles in the initiation of morphological differentiation and secondary metabolism triggered by A-factor.
AdpA 是一种全局转录调控因子，由微生物激素 A 因子诱导，激活灰色链霉菌形态分化和次生代谢所需的许多基因。我们证实，调节 tRNA 基因 bldA 是 TTA 包含的 adpA 翻译所必需的。我们还证明，AdpA 结合 bldA 启动子上游的两个位点，并激活 bldA 的转录。因此，我们揭示了灰色链霉菌中 AdpA 和 BldA 之间的独特正反馈回路。在缺乏 A 因子的突变体中强制表达 bldA 导致气生菌丝体形成和链霉素产量的部分恢复，表明正反馈回路可以防止野生型菌株中 AdpA 靶基因的过早转录激活。我们揭示了 bldA 突变体的形态缺陷主要归因于仅两个基因的 TTA 密码子：adpA 和 amfR。amfR 编码一个转录激活因子，对于气生菌丝体的形成是必不可少的，是 AdpA 调控子的成员。因此，amfR 受到涉及 AdpA 和 BldA 的前馈机制的调节。我们得出结论，由 AdpA 和 BldA 组成的中央调控单元在 A 因子触发的形态分化和次生代谢起始中发挥重要作用。
