Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza.

Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza.
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DOI:
10.1038/s41467-021-20959-1
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发表时间:
2021-01-29
影响因子:
16.6
通讯作者:
Huang L
Huang L
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ma Y;Cui G;Chen T;Ma X;Wang R;Jin B;Yang J;Kang L;Tang J;Lai C;Wang Y;Zhao Y;Shen Y;Zeng W;Peters RJ;Qi X;Guo J;Huang L

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丹参酮是中药丹参的降二萜类活性成分。这些化学物质具有特征呋喃D-环,这将它们与唇形科中经常发现的酚松香烷型二萜类化合物区分开来。然而,14,16-环氧树脂是如何形成的尚未阐明。在这里,我们报告了一个改进的基因组组装丹参使用高度纯合基因型。我们通过基因扩增分析鉴定了一个细胞色素P450(CYP 71 D)串联基因阵列。我们发现CYP 71 D373和CYP 71 D375催化碳-16(C16)羟基化和14,16-醚(杂)环化形成D环,而CYP 71 D411催化上游C20羟基化。此外,我们发现了一个大的生物合成基因簇与丹参酮的生产。共线性分析表明丹参酮在鼠尾草属植物中具有更特异的来源。阐明了唇形科松香烷型二萜和呋喃D环二萜的进化起源。丹参是一种能产生具有生物活性的丹参酮的药用植物。在这里,作者报告了改进的基因组组装,并揭示了三个CYP 71 D在催化导致形成transhinones特征呋喃D环的反应中的可能作用。
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. Salvia miltiorrhiza is a medicinal plant that can produce the bioactive tanshinones. Here, the authors report the improved genome assembly and reveal the possible roles of three CYP71Ds in catalyzing the reactions leading to the formation of the characteristic furan D-ring of transhinones.
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