Functional Divergence of Diterpene Syntheses in the Medicinal Plant Salvia miltiorrhiza
Functional Divergence of Diterpene Syntheses in the Medicinal Plant Salvia miltiorrhiza
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DOI：
10.1104/pp.15.00695
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发表时间：
2015-11-01
期刊：
影响因子：
7.4
通讯作者：
Qi, Xiaoquan
中科院分区：
文献类型：
--
作者：
Cui, Guanghong;Duan, Lixin;Qi, Xiaoquan
药用植物丹参（Salvia miltiorrhiza）产生各种丹参酮二萜类化合物，其具有药理学活性，例如血管舒张对抗缺血再灌注损伤和抗血管炎作用。它们的生物合成起始于一般的二萜类前体（E，E，E）-香叶基香叶基二磷酸，通过柯巴基二磷酸合酶（CPS）和贝壳杉烯脱氢酶样环化酶催化的顺序反应。在这里，我们报告这些酶家族的表征从S。丹参，这导致了独特的途径，包括在丹参酮生产中的作用，单独的CPS根与气生组织（SmCPS 1和SmCPS 2，分别），以及独特的生产ent-13-epi-manoyl氧化物的SmCPS 4和S。花萼片中的丹参贝壳杉烯酯酶样蛋白2。SmCPS 5是一个保守的基因，参与植物激素赤霉素的生物合成。通过RNA干扰下调SmCPS 1导致丹参酮的大量减少，代谢组学分析显示了21个潜在的中间体，表明丹参酮代谢由某些关键生物合成步骤定义的复杂网络。值得注意的是，这里观察到的CPS的保守模式和立体化学产物结果之间的相关性表明，特别是当与某些关键残基的身份相结合时，可能是预测性的相关程度。因此，这项研究提供了分子的见解功能二萜类化合物在植物中的进化多样化。
The medicinal plant Salvia miltiorrhiza produces various tanshinone diterpenoids that have pharmacological activities such as vasorelaxation against ischemia reperfusion injury and antiarrhythmic effects. Their biosynthesis is initiated from the general diterpenoid precursor (E,E,E)-geranylgeranyl diphosphate by sequential reactions catalyzed by copalyl diphosphate synthase (CPS) and kaurene synthase-like cyclases. Here, we report characterization of these enzymatic families from S. miltiorrhiza, which has led to the identification of unique pathways, including roles for separate CPSs in tanshinone production in roots versus aerial tissues (SmCPS1 and SmCPS2, respectively) as well as the unique production of ent-13-epi-manoyl oxide by SmCPS4 and S. miltiorrhiza kaurene synthase-like2 in floral sepals. The conserved SmCPS5 is involved in gibberellin plant hormone biosynthesis. Down-regulation of SmCPS1 by RNA interference resulted in substantial reduction of tanshinones, and metabolomics analysis revealed 21 potential intermediates, indicating a complex network for tanshinone metabolism defined by certain key biosynthetic steps. Notably, the correlation between conservation pattern and stereochemical product outcome of the CPSs observed here suggests a degree of correlation that, especially when combined with the identity of certain key residues, may be predictive. Accordingly, this study provides molecular insights into the evolutionary diversification of functional diterpenoids in plants.