• Tanshinones, isolated from Salvia miltiorrhiza, is efficient to treat cardiovascular and cerebrovascular diseases. Abscisic acid (ABA) treatment is found to promote tanshinone biosynthesis; however, the underlying mechanism has not been fully elucidated.
• A protein kinase namely SmAPK1 was identified as an important positive regulator of ABA-induced tanshinone accumulation in S. miltiorrhiza. Using SmAPK1 as bait, a basic region leucine zipper (bZIP) family transcription factor SmbZIP4 was screened from the cDNA library. Functional identification reveals that SmbZIP4 negatively regulates tanshinone biosynthesis in hairy roots and transgenic plants through directly targeting SmGGPPS and SmCYP76AK1.
• SmAPK1 phosphorylates the Ser97 and Thr99 site of SmbZIP4, leading to its degradation via the 26S proteasome pathway, which is promoted by ABA-induced enhancement of SmAPK1 kinase activity. Degradation of SmbZIP4 upregulates the expression levels of SmGGPPS and SmCYP76AK1, resulting in increased tanshinone content.
• Taken together, our results reveal new molecular mechanism by which SmAPK1-SmbZIP4 module plays a crucial role in ABA-induced tanshinone accumulation. This study sheds new insights in the biosynthesis of bioactive compounds in medicinal plants.

中文翻译：

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脱落酸增强 SmAPK1 介导的 SmbZIP4 磷酸化，正向调节丹参酮生物合成

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  丹参酮是从丹参中分离出来的，可有效治疗心脑血管疾病。发现脱落酸 （ABA） 处理可促进丹参酮的生物合成;然而，其潜在机制尚未完全阐明。
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  一种名为 SmAPK1 的蛋白激酶被确定为 ABA 诱导的 S. miltiorrhiza 丹参酮积累的重要正调节因子。以 SmAPK1 为诱饵，从 cDNA 文库中筛选出一个碱性区域亮氨酸拉链 （bZIP） 家族转录因子 SmbZIP4。功能鉴定显示，SmbZIP4 通过直接靶向 SmGGPPS 和 SmCYP76AK1 负向调节毛状根和转基因植物中的丹参酮生物合成。
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  SmAPK1 磷酸化 SmbZIP4 的 Ser97 和 Thr99 位点，导致其通过 26S 蛋白酶体途径降解，ABA 诱导的 SmAPK1 激酶活性增强促进其降解。SmbZIP4 的降解上调了 SmGGPPS 和 SmCYP76AK1 的表达水平，导致丹参酮含量增加。
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  综上所述，我们的结果揭示了 SmAPK1-SmbZIP4 模块在 ABA 诱导的丹参酮积累中起关键作用的新分子机制。本研究为药用植物中生物活性化合物的生物合成提供了新的见解。