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药用植物穿心莲的基因组为研究生物活性二萜 neoandrographolide 的生物合成提供了线索。

The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.

机构信息

Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, 100070, Beijing, China.

Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011-1079, USA.

出版信息

Plant J. 2019 Mar;97(5):841-857. doi: 10.1111/tpj.14162. Epub 2019 Jan 2.

DOI:10.1111/tpj.14162
PMID:30444296
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7252214/
Abstract

Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries. A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China. A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases. Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data. Gene annotation predicted 25 428 protein-coding genes. In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis. We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds. In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified. Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.

摘要

穿心莲是一种草本双子叶植物,在中国、印度和其他东南亚国家广泛用于其抗炎和抗病毒特性。在 1919 年印度流感大流行期间,穿心莲被用作关键的治疗方法,在中国仍然用于治疗传染病。穿心莲产生大量抗炎二萜内酯穿心莲内酯和新穿心莲内酯及其类似物,它们被吹捧为下一代用于肺病、肝炎、神经退行性疾病、自身免疫性疾病和炎症性皮肤病的天然抗炎药物。在这里,我们报告了一个 269 Mb 的穿心莲染色体规模基因组序列,该序列由 Illumina 短读长、PacBio 长读长和高可信度(Hi-C)数据组装而成。基因注释预测了 25428 个编码蛋白的基因。为了解开二萜生物合成的遗传基础,我们还从用茉莉酸甲酯诱导的幼苗中获得了转录组数据,这使得能够鉴定出编码二萜合酶、细胞色素 P450 单加氧酶、2-氧戊二酸依赖性双加氧酶和 UDP 依赖性糖基转移酶的基因,这些基因可能参与二萜内酯生物合成。我们进一步对一对 I 类和 II 类二萜合酶进行了功能表征,揭示了产生多样化的 labdane 相关二萜支架的能力。此外,还鉴定出一种能够催化安德拉苷 O-连接糖基化生成主要活性产物 neoandrographolide 的糖基转移酶。因此,我们的结果表明,这里生成的组合基因组和转录组数据集可用于研究重要药用植物穿心莲生物活性二萜内酯成分的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/c8301dedfb75/nihms-1582302-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/41bff89a6337/nihms-1582302-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/b4589ac37bb0/nihms-1582302-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/09c8cd4195ad/nihms-1582302-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/509ea4575fcf/nihms-1582302-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/c8301dedfb75/nihms-1582302-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/41bff89a6337/nihms-1582302-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/b4589ac37bb0/nihms-1582302-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/09c8cd4195ad/nihms-1582302-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/509ea4575fcf/nihms-1582302-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2825/7252214/c8301dedfb75/nihms-1582302-f0005.jpg

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