Xie Lihang, Chen Qiuying, Cheng Najing, Zhang Yue, Ma Yao, Zhang Yueteng, Liu Kangdong
Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China.
Front Plant Sci. 2024 Sep 26;15:1436560. doi: 10.3389/fpls.2024.1436560. eCollection 2024.
Erianin is one of the most representative bibenzyls with significant inhibitory activity against a wide range of tumor cells. However, the low erianin level in natural materials has severely inhibited its further development in health care. Our aim was to uncover the erianin biosynthetic pathway to lay the foundation for promoting its production. Firstly, we screened and obtained two species ( stems with lower erianin content and stems with higher erianin content), belonging to the same section (Chrysotoxae). A systematic analysis of bibenzyl structure and content in two stems revealed that gigantol might be an erianin biosynthetic intermediate, which was verified by introducing deuterium-labeled gigantol. Chemical structure analyses indicated that gigantol was modified by two kinds of enzymes (hydroxylases and O-methyltransferases), leading to erianin synthesis. Up-regulated hydroxylases and O-methyltransferases (OMTs) were screened out and were performed by molecular docking simulation experiments. We propose a rational biosynthetic pathway from gigantol to erianin, as well as relevant enzymes involved in the process. Our findings should significantly contribute to comprehensive resolution of the erianin biosynthetic pathway, promote its large-scale industrial production as well as contribute to biosynthesis studies of other bibenzyls.
毛兰素是最具代表性的联苄类化合物之一，对多种肿瘤细胞具有显著的抑制活性。然而，天然材料中毛兰素含量较低，严重制约了其在医疗保健领域的进一步发展。我们的目标是揭示毛兰素的生物合成途径，为促进其生产奠定基础。首先，我们筛选并获得了同属于金石斛组的两个物种（毛兰素含量较低的茎和毛兰素含量较高的茎）。对两个茎中联苄结构和含量的系统分析表明，石斛酚可能是毛兰素的生物合成中间体，这通过引入氘标记的石斛酚得到了验证。化学结构分析表明，石斛酚通过两种酶（羟化酶和O-甲基转移酶）进行修饰，从而导致毛兰素的合成。筛选出上调的羟化酶和O-甲基转移酶（OMTs），并通过分子对接模拟实验进行了研究。我们提出了一条从石斛酚到毛兰素的合理生物合成途径，以及该过程中涉及的相关酶。我们的研究结果应有助于全面解析毛兰素的生物合成途径，促进其大规模工业化生产，并为其他联苄类化合物的生物合成研究做出贡献。
