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Review
. 2023 Jan 18:14:1073848.
doi: 10.3389/fpls.2023.1073848. eCollection 2023.

Integration of high-throughput omics technologies in medicinal plant research: The new era of natural drug discovery

Wenting Zhang  1   2 , Yuan Zeng  3   4 , Meng Jiao  5 , Chanjuan Ye  6 , Yanrong Li  5 , Chuanguang Liu  6 , Jihua Wang  1   2
Affiliations
Review

Integration of high-throughput omics technologies in medicinal plant research: The new era of natural drug discovery

Wenting Zhang et al. Front Plant Sci. .

Abstract

Medicinal plants are natural sources to unravel novel bioactive compounds to satisfy human pharmacological potentials. The world's demand for herbal medicines is increasing year by year; however, large-scale production of medicinal plants and their derivatives is still limited. The rapid development of modern technology has stimulated multi-omics research in medicinal plants, leading to a series of breakthroughs on key genes, metabolites, enzymes involved in biosynthesis and regulation of active compounds. Here, we summarize the latest research progress on the molecular intricacy of medicinal plants, including the comparison of genomics to demonstrate variation and evolution among species, the application of transcriptomics, proteomics and metabolomics to explore dynamic changes of molecular compounds, and the utilization of potential resources for natural drug discovery. These multi-omics research provide the theoretical basis for environmental adaptation of medicinal plants and allow us to understand the chemical diversity and composition of bioactive compounds. Many medicinal herbs' phytochemical constituents and their potential health benefits are not fully explored. Given their large diversity and global distribution as well as the impacts of growth duration and environmental factors on bioactive phytochemicals in medicinal plants, it is crucial to emphasize the research needs of using multi-omics technologies to address basic and applied problems in medicinal plants to aid in developing new and improved medicinal plant resources and discovering novel medicinal ingredients.

Keywords: active ingredients; biosynthesis pathways; high-throughput omics; medicinal plant; phytochemicals.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Medicinal plants with complete genome sequencing. The X-axis shows the chromosome number of a medicinal plant genome. The Y-axis represents the genome size (Log4(Mb)) of each plant.
Figure 2
Figure 2
Key genes and metabolites of three phenolics compounds biosynthesis pathways in plants. The green, yellow and red background areas represent the biosynthetic pathways of phenolic acids, lignin and flavonoids, respectively. Bolded metabolites and genes represent the beginning of henylpropanoid pathway shared by phenolics compounds biosynthesis. Different flavonoids are indicated by black bold font and grouped by red rectangular boxes in each pathway. Key genes in biosynthesis pathways are in italics: PAL, phenylalanine ammonialyase; C4H, cinnamic acid 4-hydroxylase; 4CL, 4-coumarate-CoA ligase; HCT, hydroxycinnamoyl CoA shikimate hydroxycinnamoyl transferase; RAS, rosmarinic acid synthase; CYP98A, cytochrome P450-dependent monooxygenase; C3H, p-coumarate 3-hydroxylase; CHS, chalcone synthase; CH4’GT, chalcone 4’-O-glucosyltransferase; CH2’GT, chalcone 2′-glucosyltransferase; AS, aureusidin synthase; CHR, chalcone reductase; CHI, chalcone flavanone isomerase; IFS, isoflavone synthase; F3′H, favonoid 3′ hydroxylase; FNS (FNSI and FNSII), flavone synthase; F6H, flavanone-6-hydroxylase; FOMT, flavonoid O-methyltransferase; HI4’OMT, hydroxyisoflavone 4’-O-methyltransferase; HID, hydroxyisoflavanone dehydratase; DFR, dihydroflavonol 4-reductase; F3H, favanone 3-hydroxylase; F3’5’H, flavonoid-3′,5′-hydroxylase; FLS, flavonol synthase; ANS, anthocyanidin synthase (LDOX, leucoanthocyanidin dioxygenase); ANR, anthocyanidin reductase; LAR, leucoanthocyanidin reductase; UFGT, UDP glucose:flavonoid 3-O-glycosyltranferase; OMT, O-methyltransferase; CCoAOMT, caffeoyl-CoA O-methyltransferase; F5H, ferulate 5-hydroxylase; CSE, caffeoyl shikimate esterase; COMT, caffeic acid O-methyltransferase; CCR, cinnamoyl-CoA reductase; CAD, cinnamyl alcohol dehydrogenase; LAC, laccase; POD, peroxidase; TAL, tyrosine ammonia lyase; BA2H, benzoic acid 2-hydroxylase; S3H, salicylic acid 3-hydroxylase; BA4H, benzoic acid 4-hydroxylase; HBA3H, p-hydroxybenzoic acid 3-hydroxylase; PCA5H, protocatechuic acid 5-hydroxylase; PCA3OMT, protocatechuic acid 3-O-methyltransferase; VA4OMT, vanillic acid 4-O-methyltransferase; VA5H, vanillic acid 5-hydroxylase; VA5OMT, vanillic acid 5-O-methyltransferase. Naringenin chalcone and naringenin in a larger font are key primarily intermediate metabolite in flavonoid biosynthesis. Dashed arrows indicate that some unknown enzymes are involved in these processes. Scientific names are representative medicinal plants, which are exploited by various pharmaceutical companies to produce phenolics compounds.
Figure 3
Figure 3
The main contents of proteome research related to biosynthesis or accumulation of metabolites in medicinal plant.
Figure 4
Figure 4
Terpenoids synthesized by representative medicinal plants through mevalonate (MVA) and methylerythritol phosphate (MEP) pathways. The key proteins involved in the two pathways are in orange. AACT, acetoacetyl-CoA thiolase; HMGS, 3-hydroxy-3-methylglutaryl-CoA synthase; HMGR, 3-hydroxy-3-methylglutaryl-CoA reductase; MK, mevalonate kinase; PMK, phosphomevalonate kinase; MPDC, mevalonate diphosphate decarboxylase; DXS, 1-deoxy-d-xylulose 5-phosphate synthase; DXR, 1-deoxy-d-xylulose 5-phosphate reductoisomerase; MCT, 2C-methyl-d-erythritol 4-phosphate cytidyl transferase; CMK, 4-diphosphocytidyl-2C-methyl-d-erythritol kinase; MDS, 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase; HDS, 1-hydroxy-2-methyl-2-€-butenyl 4-diphosphate synthase; HDR, 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase; IPPI, Isopentenyldiphosphate-isomerase; FPPS, farnesyl diphosphate (FPP) synthase; GGPPS, geranylgeranyl diphosphate (GGPP) synthase; GPPS, geranyl diphosphate (GPP) synthase. Representative medicinal plants containing various terpenoids are listed in the blue dashed box.
Figure 5
Figure 5
Metabolic components with main pharmacodynamic function from different tissues of representative medicinal plants. Latin names are the representative medicinal plants with specific tissue(s) as the main source of medicinal ingredients.
Figure 6
Figure 6
Medicinal plant multi-omics research to facilitate drug discovery.
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Grants and funding

The preparation of this article was supported by the National Natural Science Foundation of China (31960064); the Special Fund for Introducing Scientific and Technological Talents of Guangdong Academy of Agricultural Sciences (Grant # R2021YJ-YB2008). The funder was not involved in conceptualizing this article, collecting and interpreting the information, writing or submitting the article.

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