近日，西北农林科技大学生命科学学院麻鹏达/董娟娥团队在《The Plant Journal》发表题为“The SmMYC2-SmMYB36 complex is involved in MeJA-mediated tanshinones biosynthesis in Salvia miltiorrhiza”的研究论文。 该研究揭示了茉莉酸（JA）介导的SmMYC2-SmMYB36转录复合体参与调控丹参酮生物合成的分子机制。
Tanshinone is a diterpenoid quinone derived from the roots and rhizomes of the medicinal plant Salvia miltiorrhiza. Tanshinone has a variety of biological activities and pharmacological effects, and is one of the most widely recognized natural medicines for the effective treatment of cardiovascular and cerebrovascular diseases. The market demand for tanshinone is large, while the available resources of danshen are limited, and the content of natural tanshinone is low and the content of the ingredients is unstable. Therefore, the analysis of the regulatory mechanism of exogenous environmental factors on tanshinone biosynthesis has become one of the research hotspots in this field. Previous studies have shown that methyl jasmonate (MeJA) is an effective inducer to promote tanshinone biosynthesis, and the current research on JA signaling to regulate tanshinone synthesis mainly focuses on JAZ and the transcription factors that interact with JAZ, and there are no reports on the involvement of transcription complexes in JA in regulating tanshinone synthesis. In the early stage, our group analyzed the division of labor and mechanism of Salvia miltiorrhizae JAZ family proteins in jasmonic acid-induced tanshinone and phenolic acid biosynthesis, among which SmJAZ3, SmJAZ4 and SmJAZ8 were used as negative regulators of MeJA-induced tanshinone synthesis (Pei et al. 2018, Journal of Experimental Botany; Ma et al. 2022, Horticulture Research）。 As a positive regulatory transcription factor of tanshinone synthesis, SmMYB36 contains a domain ([D/E]Lx2[R/K]x3Lx6Lx3R) that interacts with the bHLH transcription factor at its N-terminus, which can directly bind to and promote the expression of the promoters of tanshinone biosynthesis enzyme genes SmGGPPS1, SmDXS2 and SmCPS1, and indirectly promote the synthesis of tanshinone through the SmERF6 transcription factor (Ding et al. 2018, Scientific Reports; Li et al. 2023, Horticulture Research）。
In this study, the authors first identified the SmMYC2 transcription factor that interacted with SmJAZ8 through a yeast two-hybrid sieve library, and SmJAZ3 and SmJAZ4 also interacted with SmMYC2. Subsequently, SmMYC2 was found to be a positive regulator of tanshinone biosynthesis, and DAP-seq, Y1H, Dual-luc and EMSA experiments proved that the target gene of SmMYC2 was SmGGPPS1, a key enzyme gene for tanshinone biosynthesis. On this basis, the authors further found that SmMYB36 interacted with SmMYC2, and SmMYC2 and SmMYB36 synergistically promoted the biosynthesis of tanshione, and the positive regulatory effect of SmMYB36 on tanshinone depended on the presence of SmMYC2. In addition, the jasmonic acid signal inhibitor SmJAZ3/4/8 blocks the formation of the complex SmMYC2-SmMYB36 by interacting with SmMYC2 when MeJA is not present, resulting in a decrease in the activity of the SmGGPPS1 promoter, thereby hindering the biosynthesis of tanshinanone. In the presence of MeJA, SmJAZ3 and SmJAZ4 are able to be degraded by the 26S proteasome pathway, releasing the SmMYB36-SmMYC2 complex to activate SmGGPPS1 expression, thereby promoting tanshinone biosynthesis In summary, this study elucidated the dynamic regulatory mechanism of the SmJAZ3/4/8-SmMYC2-SmMYB36 module in JA signal-mediated tanshinone biosynthesis (Figure 1). This study lays a foundation for further constructing the regulatory network of JA signal-mediated tanshinone synthesis, and provides a useful tool for the efficient biomanufacturing of tanshinone.
Fig.1 The pattern of SmMYC2-SmMYB36 complex involved in JA signal-mediated tanshinone biosynthesis is shown by Dr. Ruizhi Cao, Bingbing Lv and Shuai Shao, Ph.D. students from the College of Life Sciences, Northwest A&F University, are the co-first authors of the paper. Professor Dong Juan'e and Associate Professor Ma Pengda from the School of Life Sciences of Northwest A&F University are the co-corresponding authors of the paper. Zhao Ying and Yang Mengdan, master's students of Northwest A&F University, Zuo Anqi, an undergraduate student, and Wei Jia, an assistant researcher at Jilin Academy of Agricultural Sciences, also participated in some of the work. The research was supported by the National Natural Science Foundation of China (32270278) and the University Student Science and Technology Innovation Program (S202310712297).
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