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Metabolic engineering of artificially modified transcription factor SmMYB36-VP16 for high-level production of tanshinones and phenolic acids
Metabolic Engineering ( IF 6.8 ) Pub Date : 2024-08-22 , DOI: 10.1016/j.ymben.2024.08.004 Entong Jia 1 , He Li 1 , Fang He 1 , Xiaoyu Xu 1 , Jia Wei 2 , Gaige Shao 3 , Jingying Liu 1 , Pengda Ma 1
Metabolic Engineering ( IF 6.8 ) Pub Date : 2024-08-22 , DOI: 10.1016/j.ymben.2024.08.004 Entong Jia 1 , He Li 1 , Fang He 1 , Xiaoyu Xu 1 , Jia Wei 2 , Gaige Shao 3 , Jingying Liu 1 , Pengda Ma 1
Affiliation
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:
人工修饰的转录因子 SmMYB36-VP16 的代谢工程,用于丹参酮和酚酸的高水平生产
丹参酮类和酚酸类是丹参中的两种主要化学成分,临床上用于治疗高血压、冠心病、动脉粥样硬化等多种疾病,具有广泛的药用价值。如果没有代谢途径的调控和优化,就无法实现这两种代谢产物在分离的植物组织中靶产物的高效合成,而转录因子作为植物组织代谢工程中的常见调控元件发挥着重要作用。然而,大多数调节作用是特定于一类代谢物的,或者存在两类代谢物的相反调节。本研究构建了人工修饰的转录因子 SmMYB36-VP16,以同时增强丹参根中的丹参酮和酚酸。进一步结合引子双重筛选技术,通过应用筛选出的最优引子,丹参菌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剂双重筛选技术的结合促进了植物分离的组织细胞工厂产生靶向药物代谢物的能力。这种策略可以应用于其他物种,为医药工业生产潜在的天然产品奠定基础。
更新日期:2024-08-22
中文翻译:
人工修饰的转录因子 SmMYB36-VP16 的代谢工程,用于丹参酮和酚酸的高水平生产
丹参酮类和酚酸类是丹参中的两种主要化学成分,临床上用于治疗高血压、冠心病、动脉粥样硬化等多种疾病,具有广泛的药用价值。如果没有代谢途径的调控和优化,就无法实现这两种代谢产物在分离的植物组织中靶产物的高效合成,而转录因子作为植物组织代谢工程中的常见调控元件发挥着重要作用。然而,大多数调节作用是特定于一类代谢物的,或者存在两类代谢物的相反调节。本研究构建了人工修饰的转录因子 SmMYB36-VP16,以同时增强丹参根中的丹参酮和酚酸。进一步结合引子双重筛选技术,通过应用筛选出的最优引子,丹参菌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剂双重筛选技术的结合促进了植物分离的组织细胞工厂产生靶向药物代谢物的能力。这种策略可以应用于其他物种,为医药工业生产潜在的天然产品奠定基础。