Tanshinones and phenolic acids are the two main chemical constituents in Salvia miltiorrhiza, which are used clinically for the treatment of hypertension, coronary heart disease, atherosclerosis, and many other diseases, and have broad medicinal value. The efficient synthesis of the target products of these two metabolites in isolated plant tissues cannot be achieved without the regulation and optimization of metabolic pathways, and transcription factors play an important role as common regulatory elements in plant tissue metabolic engineering. However, most of the regulatory effects are specific to one class of metabolites, or an opposing regulation of two classes of metabolites exists. In this study, an artificially modified transcription factor, SmMYB36-VP16, was constructed to enhance tanshinones and phenolic acids in Salvia miltiorrhiza hair roots simultaneously. Further in combination with the elicitors dual-screening technique, by applying the optimal elicitors screened, the tanshinones content in the transgenic hairy roots of Salvia miltiorrhiza reached 6.44 mg/g DW, which was theoretically 6.08-fold that of the controls without any treatment, and the content of phenolic acids reached 141.03 mg/g DW, which was theoretically 5.05-fold that of the controls without any treatment. The combination of artificially modified transcriptional regulatory and elicitors dual-screening techniques has facilitated the ability of plant isolated tissue cell factories to produce targeted medicinal metabolites. This strategy could be applied to other species, laying the foundation for the production of potential natural products for the medicinal industry.

中文翻译：

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人工修饰转录因子SmMYB36-VP16的代谢工程用于高水平生产丹参酮和酚酸


丹参酮和酚酸是丹参中的两种主要化学成分，临床用于治疗高血压、冠心病、动脉粥样硬化等多种疾病，具有广泛的药用价值。这两种代谢物的目标产物在分离的植物组织中的高效合成离不开代谢途径的调控和优化，而转录因子作为植物组织代谢工程中的共同调控元件发挥着重要作用。然而，大多数调节作用是针对一类代谢物的，或者存在对两类代谢物的相反调节。在本研究中，构建了人工修饰的转录因子SmMYB36-VP16，以同时增强丹参毛根中的丹参酮和酚酸。进一步结合诱导子双筛选技术，应用筛选出的最优诱导子，转基因丹参毛状根中丹参酮含量达到6.44 mg/g DW，理论上是未处理对照的6.08倍，酚酸含量达到141.03 mg/g DW，理论上是未处理对照的5.05倍。人工修饰的转录调控和激发子双重筛选技术的结合促进了植物分离的组织细胞工厂生产靶向药物代谢物的能力。该策略可以应用于其他物种，为医药工业潜在天然产品的生产奠定基础。