State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Kunming, China.
Nat Commun. 2021 Jan 29;12(1):685. doi: 10.1038/s41467-021-20959-1.
Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.
丹参酮是中药丹参（Salvia miltiorrhiza）的生物活性的非二萜类成分。这些化学物质具有呋喃 D-环的特征，这使它们与经常在唇形科中发现的酚类枞型二萜类化合物区分开来。然而，14,16-环氧的形成方式尚未阐明。在这里，我们通过使用高度纯合基因型报告了丹参的改进基因组组装。我们通过基因扩展分析鉴定出细胞色素 P450（CYP71D）串联基因阵列。我们表明 CYP71D373 和 CYP71D375 催化 C16 和 14,16-醚（杂）环化的 C16 位羟化，形成 D-环，而 CYP71D411 催化 C20 位的上游羟化。此外，我们发现了一个与丹参酮生产相关的大型生物合成基因簇。共线性分析表明，丹参属中丹参酮具有更特异的起源。它说明了唇形科中枞型二萜类化合物和呋喃 D-环化合物的进化起源。
