Multi-Omics Roadmap to Plant-Derived Medicines

Jia-Yu Xue; Si-Jie Liu; Jing Wang; Xin-Cheng Huang; Zhi-Chao Xu; Xiao-Xue Fang; Zhen Li; Yves Van de Peer

doi:10.1016/j.eng.2025.10.019

Engineering ›› DOI: 10.1016/j.eng.2025.10.019

review-article

Multi-Omics Roadmap to Plant-Derived Medicines

Jia-Yu Xue ^a^,¹
, Si-Jie Liu ^a^,¹
, Jing Wang ^b^,¹
, Xin-Cheng Huang ^a
, Zhi-Chao Xu ^b
, Xiao-Xue Fang ^b^,^*
, Zhen Li ^c^,^d^,^*
, Yves Van de Peer ^a^,^c^,^d^,^e^,^*

Author information +

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Abstract

Medicinal plants are invaluable sources of bioactive natural products or metabolites, however the discovery and sustainable utilization of these metabolites remain challenging. Genomic resources now provide a foundation for elucidating biosynthetic pathways that enable metabolic engineering and high-yield breeding. While genomic studies in medicinal plants have long lagged behind those on model species, next-generation sequencing has accelerated progress. Capitalizing on this genomic expansion, we systematically reviewed advancements in sequencing and assembly and analyzed more than 400 publicly available medicinal plant genomes. These resources, though variable in quality and phylogenetically biased (i.e., angiosperm-dominated), allow for multi-omics analysis of biosynthetic pathways. Single-cell RNA sequencing resolves cell-type-specific expression of biosynthetic genes, while emerging spatial transcriptomic and metabolomic techniques map metabolite distributions. Key findings reveal that small and large gene duplications drive the diversity of metabolites. Comparative genomics has identified copy number variations in critical enzyme families and divergent evolution of biosynthetic gene clusters. Further development of sustainable high-yield varieties of medicinal plants requires the integration of multi-omics technologies with systems biology for pathway refinement, enzyme engineering, and the deployment of genome-enabled molecular breeding.

Keywords

Medicinal plant / Plant natural products / Genomics / Multi-omics / Biosynthesis / Enzyme

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Jia-Yu Xue, Si-Jie Liu, Jing Wang, Xin-Cheng Huang, Zhi-Chao Xu, Xiao-Xue Fang, Zhen Li, Yves Van de Peer. Multi-Omics Roadmap to Plant-Derived Medicines. Engineering DOI:10.1016/j.eng.2025.10.019

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References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Li Y, Wang J, Li L, Song W, Li M, Hua X, et al.Natural products of pentacyclic triterpenoids: from discovery to heterologous biosynthesis.Nat Prod Rep 2023; 40(8):1303-1353.

[2]	Guo L, Yao H, Chen W, Wang X, Ye P, Xu Z, et al.Natural products of medicinal plants: biosynthesis and bioengineering in post-genomic era.Hortic Res 2022; 9:uhac223.

[3]	Christensen LP.Ginsenosides chemistry, biosynthesis, analysis, and potential health effects.Adv Food Nutr Res 2009; 55:1-99.

[4]	Fatt MP, Zhang MD, Kupari J, Alt Mınkök, Yang Y, Hu Y, et al.Morphine-responsive neurons that regulate mechanical antinociception. Science, 385(6712):eado6593 (2024)

[5]	Liang F, Xie Y, Zhang C, Zhao Y, Motawia MS, Kampranis SC.Elucidation of the final steps in Taxol biosynthesis and its biotechnological production.Nat Synth 2025; 4(10):1212-1222.

[6]	Tian Y, Kong L, Li Q, Wang Y, Wang Y, An Z, et al.Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids.Nat Prod Rep 2024; 41(11):1787-1810.

[7]	Song Y, Zhang Y, Wang X, Yu X, Liao Y, Zhang H, et al.Telomere-to-telomere reference genome for Panax ginseng highlights the evolution of saponin biosynthesis. Hortic Res, 11(6):uhae107 (2024)

[8]	Xu Z, Tian Y, Wang J, Ma Y, Li Q, Zhou Y, et al.Convergent evolution of berberine biosynthesis. Sci Adv, 10(48):eads3596 (2024)

[9]	Liao B, Shen X, Xiang L, Guo S, Chen S, Meng Y, et al.Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield.Mol Plant 2022; 15(8):1310-1328.

[10]	Xiong X, Gou J, Liao Q, Li Y, Zhou Q, Bi G, et al.The Taxus genome provides insights into paclitaxel biosynthesis.Nat Plants 2021; 7(8):1026-1036.

[11]	Guo L, Winzer T, Yang X, Li Y, Ning Z, He Z, et al.The opium poppy genome and morphinan production.Science 2018; 362(6412):343-347.

[12]	Liang Y, Gao Q, Li F, Du Y, Wu J, Pan W, et al.The giant genome of lily provides insights into the hybridization of cultivated lilies.Nat Commun 2025; 16(1):45.

[13]	Sun S, Shen X, Li Y, Li Y, Wang S, Li R, et al.Single-cell RNA sequencing provides a high-resolution roadmap for understanding the multicellular compartmentation of specialized metabolism.Nat Plants 2023; 9(1):179-190.

[14]	Wang YJ, Tain T, Yu JY, Li J, Xu B, Chen J, et al.Genomic and structural basis for evolution of tropane alkaloid biosynthesis.Proc Natl Acad Sci USA 2023; 120(17):e2302448120.

[15]	Ma Y, Cui G, Chen T, Ma X, Wang R, Jin B, et al.Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza.Nat Commun 2021; 12(1):685.

[16]	Du Y, Peng S, Chen H, Li J, Huang F, Chen W, et al.Unveiling the spatiotemporal landscape of Ganoderma lingzhi: insights into ganoderic acid distribution and biosynthesis. Engineering. In press.

[17]	Lynch RC, Padgitt-Cobb LK, Garfinkel AR, Knaus BJ, Hartwick NT, Allsing N, et al.Domesticated cannabinoid synthases amid a wild mosaic cannabis pangenome.Nature 2025; 643(8073):1001-1010.

[18]	Liu H, Wang X, Wang G, Cui P, Wu S, Ai C, et al.The nearly complete genome of Ginkgo biloba illuminates gymnosperm evolution.Nat Plants 2021; 7(6):748-756.

[19]	Wu S, Morotti ALM, Yang J, Wang E, Tatsis EC.Single-cell RNA sequencing facilitates the elucidation of the complete biosynthesis of the antidepressant hyperforin in St.John&’s wort. Mol Plant 2024; 17(9):1439-1457.

[20]	Xu Z, Chen S, Wang Y, Tian Y, Wang X, Xin T, et al.Crocus genome reveals the evolutionary origin of crocin biosynthesis.Acta Pharm Sin B 2024; 14(4):1878-1891.

[21]	Chen Y, Fang T, Su H, Duan S, Ma R, Wang P, et al.A reference-grade genome assembly for Astragalus mongholicus and insights into the biosynthesis and high accumulation of triterpenoids and flavonoids in its roots.Plant Commun 2023; 4(2):100469.

[22]	Tu L, Su P, Zhang Z, Gao L, Wang J, Hu T, et al.Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis.Nat Commun 2020; 11(1):971.

[23]	Kang M, Fu R, Zhang P, Lou S, Yang X, Chen Y, et al.A chromosome-level Camptotheca acuminata genome assembly provides insights into the evolutionary origin of camptothecin biosynthesis.Nat Commun 2021; 12(1):3531.

[24]	He S, Dong X, Zhang G, Fan W, Duan S, Shi H, et al.High quality genome of Erigeron breviscapus provides a reference for herbal plants in Asteraceae.Mol Ecol Resour 2021; 21(1):153-169.

[25]	Sun W, Leng L, Yin Q, Xu M, Huang M, Xu Z, et al.The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.Plant J 2019; 97(5):841-857.

[26]	Li C, Wood JC, Vu AH, Hamilton JP, Rodriguez CE Lopez, Payne RME, et al.Single-cell multi-omics in the medicinal plant Catharanthus roseus.Nat Chem Biol 2023; 19(8):1031-1041.

[27]	1K Medicinal Plant Genome Database [internet].Wuhan: Wuhan Benagen Tech Solutions Company Limited; 2018 [cited 2025 Jun 30]. Available from: http://www.herbgenome.com/.

[28]	Huang XC, Tang H, Wei X, He Y, Hu S, Wu JY, et al.The gradual establishment of complex coumarin biosynthetic pathway in Apiaceae.Nat Commun 2024; 15(1):6864.

[29]	Sanger F, Nicklen S, Coulson AR.DNA sequencing with chain-terminating inhibitors.Biotechnology 1992; 24:104-108.

[30]	Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, et al.Accurate whole human genome sequencing using reversible terminator chemistry.Nature 2008; 456(7218):53-59.

[31]	Metzker ML.Sequencing technologies—the next generation.Nat Rev Genet 2010; 11(1):31-46.

[32]	Song C, Liu Y, Song A, Dong G, Zhao H, Sun W, et al.The Chrysanthemum nankingense genome provides insights into the evolution and diversification of chrysanthemum flowers and medicinal traits.Mol Plant 2018; 11(12):1482-1491.

[33]	Alkan C, Sajjadian S, Eichler EE.Limitations of next-generation genome sequence assembly.Nat Methods 2011; 8(1):61-65.

[34]	Lieberman-Aiden E, van NL Berkum, Williams L, Imakaev M, Ragoczy T, Telling A, et al.Comprehensive mapping of long-range interactions reveals folding principles of the human genome.Science 2009; 326(5950):289-293.

[35]	Burton JN, Adey A, Patwardhan RP, Qiu R, Kitzman JO, Shendure J.Chromosome-scale scaffolding of de novo genome assemblies based on chromatin interactions.Nat Biotechnol 2013; 31(12):1119-1125.

[36]	Dudchenko O, Batra SS, Omer AD, Nyquist SK, Hoeger M, Durand NC, et al.De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds.Science 2017; 356(6333):92-95.

[37]	Lam ET, Hastie A, Lin C, Ehrlich D, Das SK, Austin MD, et al.Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly.Nat Biotechnol 2012; 30(8):771-776.

[38]	Mostovoy Y, Levy-Sakin M, Lam J, Lam ET, Hastie AR, Marks P, et al.A hybrid approach for de novo human genome sequence assembly and phasing.Nat Methods 2016; 13(7):587-590.

[39]	Zhang Y, Shen Q, Leng L, Zhang D, Chen S, Shi Y, et al.Incipient diploidization of the medicinal plant Perilla within 10 000 years.Nat Commun 2021; 12(1):5508.

[40]	Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, et al.Real-time DNA sequencing from single polymerase molecules.Science 2009; 323(5910):133-138.

[41]	Wenger AM, Peluso P, Rowell WJ, Chang PC, Hall RJ, Concepcion GT, et al.Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome.Nat Biotechnol 2019; 37(10):1155-1162.

[42]	Deamer D, Akeson M, Branton D.Three decades of nanopore sequencing.Nat Biotechnol 2016; 34(5):518-524.

[43]	Koren S, Schatz MC, Walenz BP, Martin J, Howard JT, Ganapathy G, et al.Hybrid error correction and de novo assembly of single-molecule sequencing reads.Nat Biotechnol 2012; 30(7):693-700.

[44]	Simpson JT, Workman RE, Zuzarte PC, David M, Dursi LJ, Timp W.Detecting DNA cytosine methylation using nanopore sequencing.Nat Methods 2017; 14(4):407-410.

[45]	Chin CS, Peluso P, Sedlazeck FJ, Nattestad M, Concepcion GT, Clum A, et al.Phased diploid genome assembly with single-molecule real-time sequencing.Nat Methods 2016; 13(12):1050-1054.

[46]	Nurk S, Koren S, Rhie A, Rautiainen M, Bzikadze AV, Mikheenko A, et al.The complete sequence of a human genome.Science 2022; 376(6588):44-53.

[47]	Feng Y, Zhou J, Li D, Wang Z, Peng C, Zhu G.The haplotype-resolved T2T genome assembly of the wild potato species Solanum commersonii provides molecular insights into its freezing tolerance.Plant Commun 2024; 5(10):100980.

[48]	Chen W, Yan M, Chen S, Sun J, Wang J, Meng D, et al.The complete genome assembly of Nicotiana benthamiana reveals the genetic and epigenetic landscape of centromeres.Nat Plants 2024; 10(12):1928-1943.

[49]	Rhie A, McCarthy SA, Fedrigo O, Damas J, Formenti G, Koren S, et al.Towards complete and error-free genome assemblies of all vertebrate species.Nature 2021; 592(7856):737-746.

[50]	Pollard MO, Gurdasani D, Mentzer AJ, Porter T, Sandhu MS.Long reads: their purpose and place.Hum Mol Genet 2018; 27(R2):34-41.

[51]	Logsdon GA, Vollger MR, Eichler EE.Long-read human genome sequencing and its applications.Nat Rev Genet 2020; 21(10):597-614.

[52]	Dohm JC, Lottaz C, Borodina T, Himmelbauer H.SHARCGS, a fast and highly accurate short-read assembly algorithm for de novo genomic sequencing.Genome Res 2007; 17(11):1697-1706.

[53]	Zerbino DR, Birney E.Velvet: algorithms for de novo short read assembly using de Bruijn graphs.Genome Res 2008; 18(5):821-829.

[54]	Luo R, Liu B, Xie Y, Li Z, Huang W, Yuan J, et al.SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler.Gigascience 2012; 1(1):18.

[55]	Koren S, Walenz BP, Berlin K, Miller JR, Bergman NH, Phillippy AM.Canu: scalable and accurate long-read assembly via adaptive K-mer weighting and repeat separation.Genome Res 2017; 27(5):722-736.

[56]	Chen Y, Nie F, Xie SQ, Zheng YF, Dai Q, Bray T, et al.Efficient assembly of nanopore reads via highly accurate and intact error correction.Nat Commun 2021; 12(1):60.

[57]	Cheng H, Concepcion GT, Feng X, Zhang H, Li H.Haplotype-resolved de novo assembly using phased assembly graphs with Hifiasm.Nat Methods 2021; 18(2):170-175.

[58]	Cheng H, Asri M, Lucas J, Koren S, Li H.Scalable telomere-to-telomere assembly for diploid and polyploid genomes with double graph.Nat Methods 2024; 21(6):967-970.

[59]	Belser C, Istace B, Denis E, Dubarry M, Baurens FC, Falentin C, et al.Chromosome-scale assemblies of plant genomes using nanopore long reads and optical maps.Nat Plants 2018; 4(11):879-887.

[60]	Xu S, Chen R, Zhang X, Wu Y, Yang L, Sun Z, et al.The evolutionary tale of lilies: giant genomes derived from transposon insertions and polyploidization.Innovation 2024; 5(6):100726.

[61]	Hao F, Liu X, Zhou B, Tian Z, Zhou L, Zong H, et al.Chromosome-level genomes of three key Allium crops and their trait evolution.Nat Genet 2023; 55(11):1976-1986.

[62]	Zhang G, Tian Y, Zhang J, Shu L, Yang S, Wang W, et al.Hybrid de novo genome assembly of the Chinese herbal plant Danshen (Salvia miltiorrhiza Bunge).Gigascience 2015; 4:62.

[63]	Su X, Yang L, Wang D, Shu Z, Yang Y, Chen S, et al.1K medicinal plant genome database: an integrated database combining genomes and metabolites of medicinal plants.Hortic Res 2022; 9:uhac075.

[64]	Pei T, Zhu S, Liao W, Fang Y, Liu J, Kong Y, et al.Gap-free genome assembly and CYP450 gene family analysis reveal the biosynthesis of anthocyanins in Scutellaria baicalensis.Hortic Res, 10(12):uhad235 (2023)

[65]	Chen K, Zhang M, Xu L, Yi Y, Wang L, Wang H, et al.Identification of oxidosqualene cyclases associated with saponin biosynthesis from Astragalus membranaceus reveals a conserved motif important for catalytic function.J Adv Res 2023; 43:247-257.

[66]	Michael TP, VanBuren R.Building near-complete plant genomes.Curr Opin Plant Biol 2020; 54:26-33.

[67]	Ludwiczuk A, Asakawa Y.Bryophytes as a source of bioactive volatile terpenoids—a review.Food Chem Toxicol 2019; 132:110649.

[68]	Sim FAão, Waterhouse RM, Ioannidis P, Kriventseva EV, Zdobnov EM.BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs.Bioinformatics 2015; 31(19):3210-3212.

[69]	Guan R, Zhao Y, Zhang H, Fan G, Liu X, Zhou W, et al.Draft genome of the living fossil Ginkgo biloba.Gigascience 2016; 5(1):49.

[70]	Jia KH, Liu H, Zhang RG, Xu J, Zhou SS, Jiao SQ, et al.Chromosome-scale assembly and evolution of the tetraploid Salvia splendens (Lamiaceae) genome.Hortic Res 2021; 8(1):177.

[71]	Li J, Lv M, Du L, Yunga A, Hao S, Zhang Y, et al.An enormous Paris polyphylla genome sheds light on genome size evolution and polyphyllin biogenesis.2020. bioRxiv: 2020.06.01.126920.

[72]	Niu S, Li J, Bo W, Yang W, Zuccolo A, Giacomello S, et al.The Chinese pine genome and methylome unveil key features of conifer evolution.Cell 2022; 185(1):204-217.

[73]	Liu Y, Wang S, Li L, Yang T, Dong S, Wei T, et al.The Cycas genome and the early evolution of seed plants.Nat Plants 2022; 8(4):389-401.

[74]	Fan H, Chai Z, Yang X, Liu A, Sun H, Wu Z, et al.Chromosome-scale genome assembly of Astragalus membranaceus using PacBio and Hi-C technologies.Sci Data 2024; 11(1):1071.

[75]	Bredeson JV, Lyons JB, Oniyinde IO, Okereke NR, Kolade O, Nnabue I, et al.Chromosome evolution and the genetic basis of agronomically important traits in greater yam.Nat Commun 2022; 13(1):2001.

[76]	Zhang YM, Wei ZY, Yang CA, Feng XY, Wang Y, Li SX, et al.A telomere-to-telomere genome assembly for greater yam Dioscorea alata.Plant Commun 2025; 6(7):101326.

[77]	Encyclopedia Britannica. Chicago: Britannica; 2019.

[78]	Petrovska BB.Historical review of medicinal plants’ usage.Pharmacogn Rev 2012; 6(11):1-5.

[79]	Gu S, Pei J.Innovating Chinese herbal medicine: from traditional health practice to scientific drug discovery.Front Pharmacol 2017; 8:381.

[80]	Wang H, Guo H, Wang N, Huo YX.Toward the heterologous biosynthesis of plant natural products: gene discovery and characterization.ACS Synth Biol 2021; 10(11):2784-2795.

[81]	Zhao Q, Yang J, Cui MY, Liu J, Fang Y, Yan M, et al.The reference genome sequence of Scutellaria baicalensis provides insights into the evolution of wogonin biosynthesis.Mol Plant 2019; 12(7):935-950.

[82]	Zhao Q, Zhang Y, Wang G, Hill L, Weng JK, Chen XY, et al.A specialized flavone biosynthetic pathway has evolved in the medicinal plant, Scutellaria baicalensis.Sci Adv 2016; 2(4):e1501780.

[83]	Liu Y, Fernie AR, Tohge T.Diversification of chemical structures of methoxylated flavonoids and genes encoding flavonoid-O-methyltransferases.Plants 2022; 11(4):564.

[84]	Dai Y, He M, Liu H, Zeng H, Wang K, Wang R, et al.The chromosome-scale assembly of the Salvia plebeia genome provides insight into the biosynthesis and regulation of rosmarinic acid.Plant Biotechnol J 2025; 23(5):1507-1520.

[85]	Vidana GC Gamage, Lim YY, Choo WS.Anthocyanins from Clitoria ternatea flower: biosynthesis, extraction, stability, antioxidant activity, and applications.Front Plant Sci 2021; 12:792303.

[86]	Wang J, Wang X, Ma Y, Gao R, Wang Y, An Z, et al.Lonicera caerulea genome reveals molecular mechanisms of freezing tolerance and anthocyanin biosynthesis.J Adv Res 2025; 76:293-305.

[87]	Mistry V, Darji S, Tiwari P, Sharma A.Engineering Catharanthus roseus monoterpenoid indole alkaloid pathway in yeast.Appl Microbiol Biotechnol 2022; 106(7):2337-2347.

[88]	Yamada Y, Yoshimoto T, Yoshida ST, Sato F.Characterization of the promoter region of biosynthetic enzyme genes involved in berberine biosynthesis in Coptis japonica.Front Plant Sci 2016; 7:1352.

[89]	Jia Q, Brown R, Köllner TG, Fu J, Chen X, Wong GKS, et al.Origin and early evolution of the plant terpene synthase family.Proc Natl Acad Sci USA 2022; 119(15):e2100361119.

[90]	Bureau JA, Oliva ME, Dong Y, Ignea C.Engineering yeast for the production of plant terpenoids using synthetic biology approaches.Nat Prod Rep 2023; 40(12):1822-1848.

[91]	Wang Z, Peters RJ.Tanshinones: leading the way into Lamiaceae labdane-related diterpenoid biosynthesis.Curr Opin Plant Biol 2022; 66:102189.

[92]	Guo Z, Zhou Y, Li J, Liu D, Huang Y, Zhang Y, et al.Dihydroartemisinic acid dehydrogenase-mediated alternative route for artemisinin biosynthesis.Nat Commun 2025; 16(1):3888.

[93]	Sun W, Xu Z, Song C, Chen S.Herbgenomics: decipher molecular genetics of medicinal plants.Innovation 2022; 3(6):100322.

[94]	Li P, Yan MX, Liu P, Yang DJ, He ZK, Gao Y, et al.Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution.Mol Plant 2024; 17(1):158-177.

[95]	Ji J, Han X, Zang L, Li Y, Lin L, Hu D, et al.Integrative multi-omics data provide insights into the biosynthesis of furanocoumarins and mechanisms regulating their accumulation in Angelica dahurica.Commun Biol 2025; 8(1):649.

[96]	Kashima Y, Sakamoto Y, Kaneko K, Seki M, Suzuki Y, Suzuki A.Single-cell sequencing techniques from individual to multiomics analyses.Exp Mol Med 2020; 52(9):1419-1427.

[97]	Han Y, Gao S, Muegge K, Zhang W, Zhou B.Advanced applications of RNA sequencing and challenges.Bioinform Biol Insights. 2015; 9:29-46.

[98]	Zhou P, Chen H, Dang J, Shi Z, Shao Y, Liu C, et al.Single-cell transcriptome of Nepeta tenuifolia leaves reveal differentiation trajectories in glandular trichomes.Front Plant Sci 2022; 13:988594.

[99]	Yu C, Hou K, Zhang H, Liang X, Chen C, Wang Z, et al.Integrated mass spectrometry imaging and single-cell transcriptome atlas strategies provide novel insights into taxoid biosynthesis and transport in Taxus mairei stems.Plant J 2023; 115(5):1243-1260.

[100]

Bingham GC, Lee F, Naba A, Barker TH.Spatial-omics: novel approaches to probe cell heterogeneity and extracellular matrix biology.Matrix Biol, 91–92 2020; 152-166.

[101]

Li X, Li B, Gu S, Pang X, Mason P, Yuan J, et al.Single-cell and spatial RNA sequencing reveal the spatiotemporal trajectories of fruit senescence.Nat Commun 2024; 15(1):3108.

[102]

Yu X, Liu Z, Sun X.Single-cell and spatial multi-omics in the plant sciences: technical advances, applications, and perspectives.Plant Commun 2023; 4(3):100508.

[103]

Bressan D, Battistoni G, Hannon GJ.The dawn of spatial omics. Science, 381(6657):eabq4964 (2023)

[104]

Ma Y, Li Q, Tang Y, Zhang Z, Liu R, Luo Q, et al.The architecture of silk-secreting organs during the final larval stage of silkworms revealed by single-nucleus and spatial transcriptomics.Cell Rep 2024; 43(7):114460.

[105]

Hao S, Zhu X, Huang Z, Yang Q, Liu H, Wu Y, et al.Cross-species single-cell spatial transcriptomic atlases of the cerebellar cortex. Science, 385(6716):eado3927 (2024)

[106]

Han L, Liu Z, Jing Z, Liu Y, Peng Y, Chang H, et al.Single-cell spatial transcriptomic atlas of the whole mouse brain.Neuron 2025; 113(13):2141-2160.

[107]

Fu Y, Xiao W, Tian L, Guo L, Ma G, Ji C, et al.Spatial transcriptomics uncover sucrose post-phloem transport during maize kernel development.Nat Commun 2023; 14(1):7191.

[108]

Barmukh R, Garg V, Liu H, Chitikineni A, Xin L, Henry R, et al.Spatial omics for accelerating plant research and crop improvement.Trends Biotechnol 2025; 43(8):1904-1920.

[109]

Guo X, Wang Y, Zhao C, Tan C, Yan W, Xiang S, et al.An Arabidopsis single-nucleus atlas decodes leaf senescence and nutrient allocation.Cell 2025; 188(11):2856-2871.

[110]

Liu C, Leng J, Li Y, Ge T, Li J, Chen Y, et al.A spatiotemporal atlas of organogenesis in the development of orchid flowers.Nucleic Acids Res 2022; 50(17):9724-9737.

[111]

Zhong L, Geng L, Xiang Y, Guang X, Cao L, Shi J, et al.Comparative spatial transcriptomics reveals root dryland adaptation mechanism in rice and HMGB1 as a key regulator.Mol Plant 2025; 18(5):797-819.

[112]

Yu C, Luo X, Zhang C, Xu X, Huang J, Chen Y, et al.Tissue-specific study across the stem of Taxus media identifies a phloem-specific TmMYB3 involved in the transcriptional regulation of paclitaxel biosynthesis.Plant J 2020; 103(1):95-110.

[113]

Ma S, Leng Y, Li X, Meng Y, Yin Z, Hang W.High spatial resolution mass spectrometry imaging for spatial metabolomics: advances, challenges, and future perspectives.Trends Analyt Chem 2023; 159:116902.

[114]

Yu M, Ma C, Tai B, Fu X, Liu Q, Zhang G, et al.Unveiling the regulatory mechanisms of nodules development and quality formation in Panax notoginseng using multi-omics and MALDI-MSI.J Adv Res 2025; 69:463-475.

[115]

Shen S, Zhan C, Yang C, Fernie AR, Luo J.Metabolomics-centered mining of plant metabolic diversity and function: past decade and future perspectives.Mol Plant 2023; 16(1):43-63.

[116]

Van Y de Peer, Mizrachi E, Marchal K.The evolutionary significance of polyploidy.Nat Rev Genet 2017; 18(7):411-424.

[117]

Parenicová L, de S Folter, Kieffer M, Horner DS, Favalli C, Busscher J, et al.Molecular and phylogenetic analyses of the complete MADS-box transcription factor family in Arabidopsis: new openings to the MADS world.Plant Cell 2003; 15(7):1538-1551.

[118]

Liu X, Gong Q, Zhao C, Wang D, Ye X, Zheng G, et al.Genome-wide analysis of cytochrome P450 genes in Citrus clementina and characterization of a CYP gene encoding flavonoid 3′-hydroxylase.Hortic Res, 10(2):uhac283 (2022)

[119]

Wang J, Li J, Li Z, Liu B, Zhang L, Guo D, et al.Genomic insights into longan evolution from a chromosome-level genome assembly and population genomics of longan accessions.Hortic Res 2022; 9:uhac021.

[120]

Jiao Y, Wickett NJ, Ayyampalayam S, Chanderbali AS, Landherr L, Ralph PE, et al.Ancestral polyploidy in seed plants and angiosperms.Nature 2011; 473(7345):97-100.

[121]

Edger PP, Heidel-Fischer HM, Bekaert M, Rota J, Glöckner G, Platts AE, et al.The butterfly plant arms-race escalated by gene and genome duplications.Proc Natl Acad Sci USA 2015; 112(27):8362-8366.

[122]

Bennetzen JL, Schmutz J, Wang H, Percifield R, Hawkins J, Pontaroli AC, et al.Reference genome sequence of the model plant Setaria.Nat Biotechnol 2012; 30(6):555-561.

[123]

Van Y de Peer, Ashman TL, Soltis PS, Soltis DE.Polyploidy: an evolutionary and ecological force in stressful times.Plant Cell 2020; 33(1):11-26.

[124]

Mai Y, Hu H, Ji W, Xiao Y, Zhou H, Zeng Z, et al.Evolution and functional characterization of a biosynthetic gene cluster for saponin biosynthesis in Sapindaceae.Mol Plant 2025; 18(7):1089-1093.

[125]

Sun W, Yin Q, Wan H, Gao R, Xiong C, Xie C, et al.Characterization of the horse chestnut genome reveals the evolution of aescin and aesculin biosynthesis.Nat Commun 2023; 14(1):6470.

[126]

Weng JK.The evolutionary paths towards complexity: a metabolic perspective.New Phytol 2014; 201(4):1141-1149.

[127]

Li FW, Brouwer P, Carretero-Paulet L, Cheng S, de J Vries, Delaux PM, et al.Fern genomes elucidate land plant evolution and cyanobacterial symbioses.Nat Plants 2018; 4(7):460-472.

[128]

Sakamoto T, Kawabe A, Tokida-Segawa A, Shimizu B, Takatsuto S, Shimada Y, et al.Rice CYP734As function as multisubstrate and multifunctional enzymes in brassinosteroid catabolism.Plant J 2011; 67(1):1-12.

[129]

Jiang Y, Chen H, Chen X, Köllner TG, Jia Q, Wymore TW, et al.Volatile squalene from a nonseed plant Selaginella moellendorffii: emission and biosynthesis, plant physiology and biochemistry.Plant Physiol Biochem 2015; 96:1-8.

[130]

De AR La Torre, Piot A, Liu B, Wilhite B, Weiss M, Porth I.Functional and morphological evolution in gymnosperms: a portrait of implicated gene families.Evol Appl 2020; 13(1):210-227.

[131]

Fang Y, Tai Z, Hu K, Luo L, Yang S, Liu M, et al.Comprehensive review on plant cytochrome P450 evolution: copy number, diversity, and motif analysis from chlorophyta to dicotyledoneae.Genome Biol Evol, 16(11):evae240 (2024)

[132]

Liang J, Shen Q, Wang L, Liu J, Fu J, Zhao L, et al.Rice contains a biosynthetic gene cluster associated with production of the casbane-type diterpenoid phytoalexin ent-10-oxodepressin.New Phytol 2021; 231(1):85-93.

[133]

Fang H, Shen S, Wang D, Zhang F, Zhang C, Wang Z, et al.A monocot-specific hydroxycinnamoylputrescine gene cluster contributes to immunity and cell death in rice.Sci Bull 2021; 66(23):2381-2393.

[134]

Kilgore MB, Holland CK, Jez JM, Kutchan TM.Identification of a noroxomaritidine reductase with amaryllidaceae alkaloid biosynthesis related activities.J Biol Chem 2016; 291(32):16740-16752.

[135]

Liu SJ, Liu Z, Shao BY, Li T, Zhu X, Wang R, et al.Deciphering the biosynthetic pathway of triterpene saponins in Prunella vulgaris.Plant J 2025; 121(2):e17220.

[136]

Zhang W, Li J, Dong Y, Huang Y, Qi Y, Bai H, et al.Genome-wide identification and expression of BAHD acyltransferase gene family shed novel insights into the regulation of linalyl acetate and lavandulyl acetate in lavender.J Plant Physiol 2024; 292:154143.

[137]

Chen YC, Li Z, Zhao YX, Gao M, Wang JY, Liu KW, et al.The Litsea genome and the evolution of the laurel family.Nat Commun 2020; 11(1):1675.

[138]

Tian XC, Guo JF, Yan XM, Shi TL, Nie S, Zhao SW, et al.Unique gene duplications and conserved microsynteny potentially associated with resistance to wood decay in the Lauraceae.Front Plant Sci 2023; 14:1122549.

[139]

Yan XM, Zhou SS, Liu H, Zhao SW, Tian XC, Shi TL, et al.Unraveling the evolutionary dynamics of the TPS gene family in land plants.Front Plant Sci 2023; 14:1273648.

[140]

Van J Etten, Bhattacharya D.Horizontal gene transfer in eukaryotes: not if, but how much?.Trends Genet 2020; 36(12):915-925.

[141]

Soucy SM, Huang J, Gogarten JP.Horizontal gene transfer: building the web of life.Nat Rev Genet 2015; 16(8):472-482.

[142]

Widhalm JR, Ducluzeau AL, Buller NE, Elowsky CG, Olsen LJ, Basset GJC.Phylloquinone (vitamin K1) biosynthesis in plants: two peroxisomal thioesterases of lactobacillales origin hydrolyze 1,4-dihydroxy-2-naphthoyl-coa.Plant J 2012; 71(2):205-215.

[143]

Jia Q, Li G, Köllner TG, Fu J, Chen X, Xiong W, et al.Microbial-type terpene synthase genes occur widely in nonseed land plants, but not in seed plants.Proc Natl Acad Sci USA 2016; 113(43):12328-12333.

[144]

de S Vries, Fürst-Jansen JMR, Irisarri I, Dhabalia A Ashok, Ischebeck T, Feussner K, et al.The evolution of the phenylpropanoid pathway entailed pronounced radiations and divergences of enzyme families.Plant J 2021; 107(4):975-1002.

[145]

Emiliani G, Fondi M, Fani R, Gribaldo S.A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land.Biol Direct 2009; 4(1):7.

[146]

Jia X, Zhang X, Chen X, Fernie AR, Wen W.The horizontally transferred gene, CsMTAN, rewired purine traffic to build caffeine factories in tea leaves.J Integr Plant Biol 2025; 2025:1-15.

[147]

Huang X, Wang W, Gong T, Wickell D, Kuo LY, Zhang X, et al.The flying spider-monkey tree fern genome provides insights into fern evolution and arborescence.Nat Plants 2022; 8(5):500-512.

[148]

Celedon JM, Whitehill JGA, Madilao LL, Bohlmann J.Gymnosperm glandular trichomes: expanded dimensions of the conifer terpenoid defense system.Sci Rep 2020; 10(1):12464.

[149]

Li H, Li J, Li X, Li J, Chen D, Zhang Y, et al.Genomic investigation of plant secondary metabolism: insights from synteny network analysis of oxidosqualene cyclase flanking genes.New Phytol 2025; 245(5):2150-2169.

[150]

Cheng LT, Wang ZL, Zhu QH, Ye M, Ye CY.A long road ahead to reliable and complete medicinal plant genomes.Nat Commun 2025; 16(1):2150.

[151]

Feng X, Chen Q, Wu W, Wang J, Li G, Xu S, et al.Genomic evidence for rediploidization and adaptive evolution following the whole-genome triplication.Nat Commun 2024; 15(1):1635.

[152]

Cox KL Jr, Gurazada SGR, Duncan KE, Czymmek KJ, Topp CN, Meyers BC.Organizing your space: the potential for integrating spatial transcriptomics and 3D imaging data in plants.Plant Physiol 2021; 188(2):703-712.

[153]

Alexandrov T.Spatial metabolomics: from a niche field towards a driver of innovation.Nat Metab 2023; 5(9):1443-1445.

[154]

Yin R, Xia K, Xu X.Spatial transcriptomics drives a new era in plant research.Plant J 2023; 116(6):1571-1581.

[155]

Dong Y, Aharoni A.Image to insight: exploring natural products through mass spectrometry imaging.Nat Prod Rep 2022; 39(7):1510-1530.

[156]

Tu Y.The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine.Nat Med 2011; 17(10):1217-1220.

[157]

Helf MJ, Buntin K, Klan Ačar, Rust M, Petersen F, Pistorius D, et al.Scaling up for success: from bioactive natural products to new medicines.Nat Prod Rep 2024; 41(12):1824-1834.

[158]

Wang X, Chen N, Cruz-Morales P, Zhong B, Zhang Y, Wang J, et al.Elucidation of genes enhancing natural product biosynthesis through co-evolution analysis.Nat Metab 2024; 6(5):933-946.

[159]

Mehta N, Meng Y, Zare R, Kamenetsky-Goldstein R, Sattely E.A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes.Cell 2024; 187(20):5620-5637.

[160]

Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, et al.High-level semi-synthetic production of the potent antimalarial artemisinin.Nature 2013; 496(7446):528-532.

[161]

Wang YJ, Huang JP, Tian T, Yan Y, Chen Y, Yang J, et al.Discovery and engineering of the cocaine biosynthetic pathway.J Am Chem Soc 2022; 144(48):22000-22007.

[162]

Yang X, Wang Y, Byrne R, Schneider G, Yang S.Concepts of artificial intelligence for computer-assisted drug discovery.Chem Rev 2019; 119(18):10520-10594.

[163]

Arul N Murugan, Ruba G Priya, Narahari G Sastry, Markidis S.Artificial intelligence in virtual screening: models versus experiments.Drug Discov Today 2022; 27(7):1913-1923.

[164]

Mullowney MW, Duncan KR, Elsayed SS, Garg N, van JJJ der Hooft, Martin NI, et al.Artificial intelligence for natural product drug discovery.Nat Rev Drug Discov 2023; 22(11):895-916.

[165]

Wang H, Xie M, Rizzi G, Li X, Tan K, Fussenegger M.Identification of sclareol as a natural neuroprotective Cav1.3-antagonist using synthetic Parkinson-mimetic gene circuits and computer-aided drug discovery. Adv Sci, 9(7):2102855 (2022)

[166]

Xia J, Gan Z, Zhang J, Dong M, Liu S, Cui B, et al.Geometric-aware deep learning enables discovery of bifunctional ligand-based liposomes for tumor targeting therapy.Nano Today 2025; 61:102668.

[167]

Chen J, Guo S, Hu X, Wang R, Jia D, Li Q, et al.Whole-genome and genome-wide association studies improve key agricultural traits of safflower for industrial and medicinal use.Hortic Res, 10(11):uhad197 (2023)

[168]

Hsu CT, Chiu CC, Hsiao PY, Lin CY, Cheng S, Lin YC, et al.Transgene-free CRISPR/Cas9-mediated gene editing through protoplast-to-plant regeneration enhances active compounds in Salvia miltiorrhiza.Plant Biotechnol J 2024; 22(6):1549-1551.

[169]

Tian M, Luo L, Jin B, Liu J, Chen T, Tang J, et al.Highly efficient Agrobacterium rhizogenes-mediated gene editing system in Salvia miltiorrhiza inbred line bh2-7.Plant Biotechnol J 2025; 23(6):2406-2417.

[170]

Xu S, Li F, Zhou F, Li J, Cai S, Yang S, et al.Efficient targeted mutagenesis in tetraploid Pogostemon cablin by the CRISPR/Cas9-mediated genomic editing system. Hortic Res, 11(3):uhae021 (2024)