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First author: Lichan Tu; Affiliations: Capital Medical University (首都医科大学): Beijing, China
Corresponding author: Wei Gao
Triptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.
雷公藤甲素是雷公藤的一种微量天然产物。雷公藤甲素具有抗肿瘤活性,尤其是针对胰腺癌细胞。鉴定雷公藤甲素生物合成相关基因及通路是异源生物合成的先决条件。本文中,作者报道了雷公藤的参考级别基因组,contig N50长4.36 Mb。作者发现雷公藤甲素生物合成通路基因的拷贝数目受到近期的一次全基因组三倍化事件的影响。作者进一步通过整合基因组、转录组以及代谢组的数据构建了一个基因-代谢物网络。通过以上的分析,作者鉴定到了一个细胞色素P450蛋白CYP728B70在雷公藤甲素生物合成过程中催化脱氢松香酸上的一个甲基氧化形成羧基。本文的所提供的雷公藤基因组资源以及鉴定的雷公藤甲素合成候选基因为充分理解雷公藤甲素的生物合成途径和以及异源生物生产奠定了基础。
通讯:高伟 (http://scbps.ccmu.edu.cn/szdw_7817/js_7819/99200.htm)
研究方向:中药资源与分子生药学研究,主要集中在中药活性成分及天然药物基因功能鉴定、生源途径解析及合成生物学等研究领域。
doi: https://doi.org/10.1038/s41467-020-14776-1
Journal: Nature Communications
Published date: February 20, 2020
p.s. 雷公藤还有一个次生代谢产物很有意思,叫Celastrol,雷公藤红素,2006年,Yang等人发现Celastrol在小鼠体内实验中能够通过控制癌细胞的蛋白酶体进而诱发癌细胞的凋亡(Cancer Research;doi: 10.1158/0008-5472.CAN-05-4529);2015年,Liu等人发现Celastrol是一种有效的抗肥胖剂(Cell;doi: 10.1016/j.cell.2015.05.011);2017年,Guo等人发现Celastrol在大鼠模型中有效治疗肾小球膜增生性肾小球肾炎(Nature Communications;doi: 10.1038/s41467-017-00834-8)。
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