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Background Heterologous synthesis presents a promising new approach for accessing the active ingredients of traditional Chinese medicine (TCM), contributing to the conservation of natural medicinal resources. Compound Danshen preparation, a widely used TCM formulation, is designed to treat coronary heart disease and angina pectoris. It is primarily composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen), Notoginseng Radix et Rhizoma (Sanqi), and borneol (Bingpian). Danshen primarily yields tanshinones and phenolic acids, while Sanqi produces notoginsenosides. Borneol serves as an auxiliary agent to promote mental clarity, dissipate heat, and relieve pain. Objectives The objective is to employ heterologous synthesis in a single yeast strain to produce the active ingredients of Compound Danshen preparation, and these include notoginsenosides, tanshinones, and borneol. Methods Firstly, the “plug-and-play” terpene synthase screening framework in Saccharomyces cerevisiae was used for the identification of a novel, highly efficient bornyl diphosphate synthase. Furthermore, by leveraging the Compound Danshen preparation as a basis to concurrently reconstruct the biosynthetic pathways for the notoginsenoside precursor protopanaxadiol (a triterpene), the tanshinone precursor miltiradiene (a diterpene), and borneol (a monoterpene) within a single yeast strain. Results This engineered strain, termed Compound Danshen Yeast 1.0, successfully produced protopanaxadiol at 62.34 mg/L, miltiradiene at 15.38 mg/L, and borneol at 2.54 mg/L in shake-flask fermentation. Conclusions This research signifies the inaugural cross-species and multicomponent synthetic biology endeavor that enables the synthesis of active ingredients in engineered cells, setting the stage for the industrial manufacture of TCM compounds.
Background Heterologous synthesis presents a promising new approach for accessing the active ingredients of traditional Chinese medicine (TCM), contributing to the conservation of natural medicinal resources. Compound Danshen preparation, a widely used TCM formulation, is designed to treat coronary heart disease and angina pectoris. It is primarily composed of Salviae Miltiorrhizae Radix et Rhizoma (Danshen), Notoginseng Radix et Rhizoma (Sanqi), and borneol (Bingpian). Danshen primarily yields tanshinones and phenolic acids, while Sanqi produces notoginsenosides. Borneol serves as an auxiliary agent to promote mental clarity, dissipate heat, and relieve pain. Objectives The objective is to employ heterologous synthesis in a single yeast strain to produce the active ingredients of Compound Danshen preparation, and these include notoginsenosides, tanshinones, and borneol. Methods Firstly, the “plug-and-play” terpene synthase screening framework in Saccharomyces cerevisiae was used for the identification of a novel, highly efficient bornyl diphosphate synthase. Furthermore, by leveraging the Compound Danshen preparation as a basis to concurrently reconstruct the biosynthetic pathways for the notoginsenoside precursor protopanaxadiol (a triterpene), the tanshinone precursor miltiradiene (a diterpene), and borneol (a monoterpene) within a single yeast strain. Results This engineered strain, termed Compound Danshen Yeast 1.0, successfully produced protopanaxadiol at 62.34 mg/L, miltiradiene at 15.38 mg/L, and borneol at 2.54 mg/L in shake-flask fermentation. Conclusions This research signifies the inaugural cross-species and multicomponent synthetic biology endeavor that enables the synthesis of active ingredients in engineered cells, setting the stage for the industrial manufacture of TCM compounds.
Rhubarb, the Rhei radix et rhizoma (Da huang) is a member of the Polygonaceae family, included in the 2020 edition of the Chinese Pharmacopoeia, and is mainly distributed in Gansu, Sichuan, Qinghai, northwestern Yunnan, and eastern Tibet. Rhei radix et rhizoma is one of the most commonly used traditional Chinese medicines, processed into drinkable tablets in different concoctions for clinical use. Phytochemical studies showed that more than 170 compounds were isolated and identified from Rhei radix et rhizoma, including anthraquinones/anthrones (major constituents), stilbenes, chromones, flavonoids, tannins, and other compounds, etc. Rhei radix et rhizoma is an herb with a long history of traditional use and many potential therapeutic benefits. It can play the role of diarrhea, clearing heat in response to different combinations and concoctions. It is mainly used for the treatment of constipation, gastrointestinal function impairment, and other diseases. In addition, Rhei radix et rhizoma has significant antitumor, anti-inflammatory, antibacterial, hepato-renal protective, neuroprotective, hypolipidemic, and immunomodulatory activities. Its active constituents have anti-tumor, anti-inflammatory, anti-inflammatory and hepato-kidney protective properties. Although it is primarily used for gastrointestinal disorders, it may also have wider applications in various inflammatory and liver disorders. Therefore, further studies are needed to explore its full potential and mechanism of action. This paper reviews the research progress of Rhei radix et rhizoma in terms of botany, traditional use, chemistry, pharmacology, and clinical studies. It aims to provide a scientific basis for in-depth research and development of Rhei radix et rhizome resources.
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