Metabolome and transcriptome association study reveals biosynthesis of specialized benzylisoquinoline alkaloids in Phellodendron amurense

IF 4.7 4区医学 Q1 CHEMISTRY, MEDICINAL

Chinese Herbal Medicines Pub Date : 2025-01-01 DOI:10.1016/j.chmed.2024.11.003

Tingxia Liu , Wanran Zhang , Sijia Wang , Ya Tian , Yifan Wang , Ranran Gao , Shilin Chen , Wei Sun , Wei Ma , Zhichao Xu

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引用次数: 0

Abstract

Objective

Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens.

Methods

The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity.

Results

The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine.

Conclusion

Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.

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代谢组学和转录组学关联研究揭示了黄柏中特异性苯基异喹啉生物碱的生物合成

目的探讨苯基异喹啉生物碱的药理作用及临床应用。偏倚主要分布在毛茛目和柏属植物中。对毛茛属植物BIA的生物合成进行了深入的研究。然而，黄柏中BIAs的积累机制在很大程度上是未知的。本研究旨在揭示黄柏中BIAs的生物合成途径。方法对18个不同组织的金银花转录组和代谢组数据进行测序和分析。加权基因共表达网络分析（Weighted gene co-expression network analysis， WGCNA）是一种功能强大的系统生物学方法，可促进共表达网络的构建和后续分析，该方法被用于识别参与BIAs生物合成的候选基因。随后，含候选基因的重组质粒在大肠杆菌中表达，大肠杆菌是一种广泛使用的原核表达系统。这项基因工程的目的是在细菌中表达候选基因，从而能够评估所得酶的活性。结果每个同源位点的同义替换表明至少发生了一次全基因组重复事件。提出了紫金花潜在的BIA生物合成途径，并筛选出2个PR10/Bet v1成员、14个cyp450和33个甲基转移酶与BIA生物合成相关。其中一个PR10/ betv1被鉴定为去甲氯氨合酶，该酶能催化多巴胺和4-羟基苯乙醛生成(S)-去甲氯氨合酶。结论本研究为非毛茛属植物的生物合成和进化提供了重要的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chinese Herbal Medicines CHEMISTRY, MEDICINAL-

CiteScore

4.40

自引率

5.30%

发文量

629

审稿时长

10 weeks

期刊介绍： Chinese Herbal Medicines is intended to disseminate the latest developments and research progress in traditional and herbal medical sciences to researchers, practitioners, academics and administrators worldwide in the field of traditional and herbal medicines. The journal's international coverage ensures that research and progress from all regions of the world are widely included. CHM is a core journal of Chinese science and technology. The journal entered into the ESCI database in 2017, and then was included in PMC, Scopus and other important international search systems. In 2019, CHM was successfully selected for the “China Science and Technology Journal Excellence Action Plan” project, which has markedly improved its international influence and industry popularity. CHM obtained the first impact factor of 3.8 in Journal Citation Reports (JCR) in 2023.