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Identification of key genes associated with secondary metabolites biosynthesis by system network analysis in Valeriana officinalis

  • Regular Paper – Biophysics/Theoretical and Systems Biology
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Abstract

Valeriana officinalis is a medicinal plant, a source of bioactive chemical compounds and secondary metabolites which are applied in pharmaceutical industries. The advent of ethnomedicine has provided alternatives for disease treatment and has increased demands for natural products and bioactive compounds. A set of preliminary steps to answers for such demands can include integrative omics for systems metabolic engineering, as an approach that contributes to the understanding of cellular metabolic status. There is a growing trend of this approach for genetically engineering metabolic pathways in plant systems, by which natural and synthetic compounds can be produced. As in the case of most medicinal plants, there are no sufficient information about molecular mechanisms involved in the regulation of metabolic pathways in V. officinalis. In this research, systems biology was performed on the RNA-seq transcriptome and metabolome data to find key genes that contribute to the synthesis of major secondary metabolites in V. officinalis. The R Package Weighted Gene Co-Expression Network Analysis (WGCNA) was employed to analyze the data. Based on the results, some major modules and hub genes were identified to be associated with the valuable secondary metabolites. In addition, some TF-encoding genes, including AP2/ERF-ERF, WRKY and NAC TF families, as well as some regulatory factors including protein kinases and transporters were identified. The results showed that several novel hub genes, such as PCMP-H24, RPS24B, ANX1 and PXL1, may play crucial roles in metabolic pathways. The current findings provide an overall insight into the metabolic pathways of V. officinalis and can expand the potential for engineering genome-scale pathways and systems metabolic engineering to increase the production of bioactive compounds by plants.

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References

  • Abdi AI, Carvalho TG, Wilkes JM, Doerig C (2013) A secreted Plasmodium falciparum kinase reveals a signature motif for classification of tyrosine kinase-like kinases. Microbiology 159:2533–2547

    Article  CAS  PubMed  Google Scholar 

  • Alves MS, Dadalto SP, Gonçalves AB, De Souza GB, Barros VA, Fietto LG (2013) Plant bZIP transcription factors responsive to pathogens: a review. Int J Mol Sci 14:7815–7828

    Article  PubMed  PubMed Central  Google Scholar 

  • Arai H, Yanagiura K, Toyama Y, Morohashi K (2019) Genome-wide analysis of MpBHLH12, a IIIf basic helix-loop-helix transcription factor of Marchantia polymorpha. J Plant Res 132:197–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baba AI, Rigó G, Andrási N, Tietz O, Palme K, Szabados L, Cséplő Á (2019) Striving towards abiotic stresses: role of the plant CDPK superfamily members. In: Palocz-Andresen M, Szalay D, Gosztom A, Sípos L, Taligás T (eds) International climate protection. Springer, Berlin, pp 99–105

    Chapter  Google Scholar 

  • Boerjan W, Ralph J, Baucher M (2003) Lignin biosynthesis. Ann Rev Plant Biol 54:519–546

    Article  CAS  Google Scholar 

  • Degli Esposti D, Almunia C, Guery M-A, Koenig N, Armengaud J, Chaumot A, Geffard O (2019) Co-expression network analysis identifies gonad-and embryo-associated protein modules in the sentinel species Gammarus fossarum. Sci Rep 9:1–10

    Article  CAS  Google Scholar 

  • Demurtas OC, de Brito FR, Martinoia E, Giuliano G (2020) Transportomics for the characterization of plant apocarotenoid transmembrane transporters. In: Rodríguez-Concepción M, Welsch R (eds) Plant and food carotenoids. Springer, New York, pp 89–99

    Chapter  Google Scholar 

  • Do THT, Martinoia E, Lee Y (2018) Functions of ABC transporters in plant growth and development. Curr Opin Plant Biol 41:32–38

    Article  CAS  PubMed  Google Scholar 

  • Dorovkov MV, Ryazanov AG (2004) Phosphorylation of annexin I by TRPM7 channel-kinase. J Biol Chem 279:50643–50646

    Article  CAS  PubMed  Google Scholar 

  • Fatima A, Connaughton RM, Weiser M, Murphy AM, O’Grada C, Ryan M, Brennan L, O’Gaora P, Roche HM (2018) Weighted gene co-expression network analysis identifies gender specific modules and hub genes related to metabolism and inflammation in response to an acute lipid challenge. Mol Nutr Food Res 62:1700388

    Article  Google Scholar 

  • Fernández S, Wasowski C, Paladini AC, Marder M (2004) Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis. Pharm Biochem Behav 77:399–404

    Article  Google Scholar 

  • Gao X, Cox KL Jr, He P (2014) Functions of calcium-dependent protein kinases in plant innate immunity. Plants 3:160–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gish LA, Clark SE (2011) The RLK/Pelle family of kinases. Plant J 66:117–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gongora-Castillo E, Childs KL, Fedewa G, Hamilton JP, Liscombe DK, Magallanes-Lundback M, Mandadi KK, Nims E, Runguphan W, Vaillancourt B (2012) Development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species. PLoS ONE 7:e52506

  • Han X, Xu C, Zhang Q, Jiang B, Zheng J, Jiang D (2018) C2H2 transcription factor brlA regulating conidiation and affecting growth and biosynthesis of secondary metabolites in Aspergillus clavatus. Int J Agric Biol 20:2549–2555

    Google Scholar 

  • Hirsch S, Oldroyd GED (2009) GRAS-domain transcription factors that regulate plant development. Plant Signal Behav 4:698–700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodžić E, Balaban M, Šuškalo N, Galijašević S, Hasanagić D, Kukavica B (2019) Antioxidative response of Melissa officinalis L. and Valeriana officinalis L. leaves exposed to exogenous melatonin and excessive zinc and cadmium levels. J Serbian Chem Soc 84:11–25

    Article  Google Scholar 

  • Hur M, Campbell AA, Almeida-de-Macedo M, Li L, Ransom N, Jose A, Crispin M, Nikolau BJ, Wurtele ES (2013) A global approach to analysis and interpretation of metabolic data for plant natural product discovery. Nat Prod Rep 30:565–583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji G, Zheng J, Shen Y, Wu X, Jiang R, Lin Y, Loke JC, Davis KM, Reese GJ, Li QQ (2007) Predictive modeling of plant messenger RNA polyadenylation sites. BMC Bioinform 8:1–15

    Article  Google Scholar 

  • Jung CG, Hwang S-G, Park YC, Park HM, Kim DS, Park DH, Jang CS (2015) Molecular characterization of the cold-and heat-induced Arabidopsis PXL1 gene and its potential role in transduction pathways under temperature fluctuations. J Plant Physiol 176:138–146

    Article  CAS  PubMed  Google Scholar 

  • Kangasjärvi S (2019) Pic1, counteracting plant immunity signalling. Biochem J 476:2347–2350

    Article  PubMed  Google Scholar 

  • Li G, Tian Y, Yang C (2014) Research situation of GRAS family transcription factor in plants. J Anhui Agric Sci 42:4207–4210

    CAS  Google Scholar 

  • Liu W, Lin L, Zhang Z, Liu S, Gao Q, Lv Y, Tao H, He H (2019a) Gene co-expression network analysis identifies trait-related modules in Arabidopsis thaliana. Planta 249:1487–1501

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Li M, Fang X, Shen L, Yao W, Fang Z, Chen J, Feng X, Hu L, Zeng Z (2019b) Identification of surrogate prognostic biomarkers for allergic asthma in nasal epithelial brushing samples by WGCNA. J Cell Biochem 120:5137–5150

    Article  CAS  PubMed  Google Scholar 

  • Lu S, Zhang Y, Zhu K, Yang W, Ye J, Chai L, Xu Q, Deng X (2018) The citrus transcription factor CsMADS6 modulates carotenoid metabolism by directly regulating carotenogenic genes. Plant Physiol 176:2657–2676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv H, Li J, Wu Y, Garyali S, Wang Y (2016) Transporter and its engineering for secondary metabolites. Appl Microbiol Biotechnol 100:6119–6130

    Article  CAS  PubMed  Google Scholar 

  • Meinhart AD, Damin FM, Caldeirão L, da Silveira TFF, Teixeira Filho J, Godoy HT (2017) Chlorogenic acid isomer contents in 100 plants commercialized in Brazil. Food Res Int 99:522–530

    Article  CAS  PubMed  Google Scholar 

  • Nandhini S, Narayanan K, Ilango K (2018) Valeriana officinalis: a review of its traditional uses, phytochemistry and pharmacology. Asian J Pharm Clin Res 11:36–41

    Article  Google Scholar 

  • Olsen AN, Ernst HA, Leggio LL, Skriver K (2005) NAC transcription factors: structurally distinct, functionally diverse. Trends Plant Sci 10:79–87

    Article  CAS  PubMed  Google Scholar 

  • Padmanabhan M, Cournoyer P, Dinesh-Kumar S (2009) The leucine-rich repeat domain in plant innate immunity: a wealth of possibilities. Cell Microbiol 11:191–198

    Article  CAS  PubMed  Google Scholar 

  • Park YJ, Li X, Noh SJ, Kim JK, Lim SS, Park NI, Kim S, Kim YB, Kim YO, Lee SW, Arasu MV, Al-Dhabi NA, Park SU (2016) Transcriptome and metabolome analysis in shoot and root of Valeriana fauriei. BMC Genom 17:303

    Article  Google Scholar 

  • Patra B, Schluttenhofer C, Wu Y, Pattanaik S, Yuan L (2013) Transcriptional regulation of secondary metabolite biosynthesis in plants. BBA Gene Regul Mech 1829:1236–1247

    CAS  Google Scholar 

  • Paul P, Singh SK, Patra B, Liu X, Pattanaik S, Yuan L (2020) Mutually regulated AP2/ERF gene clusters modulate biosynthesis of specialized metabolites in plants. Plant Physiol 182:840–856

    Article  CAS  PubMed  Google Scholar 

  • Penzkofer M, Baron A, Naumann A, Krähmer A, Schulz H, Heuberger H (2018) Characterization of essential oil distribution in the root cross-section of Valeriana officinalis L. s.l. by using histological imaging techniques. Plant Methods 14:1–15

    Article  Google Scholar 

  • Roytrakul S, Verpoorte R (2007) Role of vacuolar transporter proteins in plant secondary metabolism: Catharanthus roseus cell culture. Phytochem Rev 6:383–396

    Article  CAS  Google Scholar 

  • Saier MH Jr, Tran CV, Barabote RD (2006) TCDB: the transporter classification database for membrane transport protein analyses and information. Nucleic Acids Res 34:D181–D186

    Article  CAS  PubMed  Google Scholar 

  • Saier MH Jr, Yen MR, Noto K, Tamang DG, Elkan C (2009) The transporter classification database: recent advances. Nucleic Acids Res 37:D274–D278

    Article  CAS  PubMed  Google Scholar 

  • Schütze K, Harter K, Chaban C (2008) Post-translational regulation of plant bZIP factors. Trends Plant Sci 13:247–255

    Article  PubMed  Google Scholar 

  • Sharma A, Amin D, Sankaranarayanan A, Arora R, Mathur AK (2020) Present status of Catharanthus roseus monoterpenoid indole alkaloids engineering in homo-and hetero-logous systems. Biotechnol Lett 42:11–23

    Article  CAS  PubMed  Google Scholar 

  • Shen D, Dong Y, Wei Y, Zhang M, Wang J, Tang Z, Xia Q, Nyawira KT, Jing M, Dou D (2019) Genome-wide and functional analyses of tyrosine kinase-like family genes reveal potential roles in development and virulence in mosquito pathogen Pythium guiyangense. Fungal Genet Biol 130:11–18

    Article  CAS  PubMed  Google Scholar 

  • Shi S, Li S, Asim M, Mao J, Xu D, Ullah Z, Liu G, Wang Q, Liu H (2018) The Arabidopsis calcium-dependent protein kinases (CDPKs) and their roles in plant growth regulation and abiotic stress responses. Int J Mol Sci 19:1900

    Article  PubMed Central  Google Scholar 

  • Shitan N (2016) Secondary metabolites in plants: transport and self-tolerance mechanisms. Biosci Biotechnol Biochem 80:1283–1293

    Article  CAS  PubMed  Google Scholar 

  • Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P (2016) The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res 45:D362–D368

    Article  PubMed  PubMed Central  Google Scholar 

  • Tahmasebi A, Aram F, Pakniyat H, Niazi A, Tavakol E, Ebrahimie E (2018) Global analysis of gene expression and identification of modules in Echinacea purpurea using systems biology approach. J Cell Mol Res 10:18–26

    CAS  Google Scholar 

  • Tahmasebi A, Ebrahimie E, Pakniyat H, Ebrahimi M, Mohammadi-Dehcheshmeh M (2019) Insights from the Echinacea purpurea (L.) Moench transcriptome: global reprogramming of gene expression patterns towards activation of secondary metabolism pathways. Ind Crops Prod 132:365–376

    Article  CAS  Google Scholar 

  • Valderrama-Martín JM, Ortigosa F, Avila C, Canovas-Ramos FM, Cañas RA (2019) Study of the NPF and NRT transporter families in the conifer Pinus pinaster. SEBBM 328

  • Valmonte GR, Arthur K, Higgins CM, MacDiarmid RM (2014) Calcium-dependent protein kinases in plants: evolution, expression and function. Plant Cell Physiol 55:551–569

    Article  CAS  PubMed  Google Scholar 

  • Vom Endt D, Kijne JW, Memelink J (2002) Transcription factors controlling plant secondary metabolism: what regulates the regulators? Phytochemistry 61:107–114

    Article  Google Scholar 

  • Williams D, Qu Y, Simionescu R, De Luca V (2019) The assembly of (+)-vincadifformine-and (−)-tabersonine-derived monoterpenoid indole alkaloids in Catharanthus roseus involves separate branch pathways. Plant J 99:626–636

    Article  CAS  PubMed  Google Scholar 

  • Yamada Y, Koyama T, Sato F (2011) Basic helix-loop-helix transcription factors and regulation of alkaloid biosynthesis. Plant Signal Behav 6:1627–1630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan J, Su P, Wei Z, Nevo E, Kong L (2017) Genome-wide identification, classification, evolutionary analysis and gene expression patterns of the protein kinase gene family in wheat and Aegilops tauschii. Plant Mol Biol 95:227–242

    Article  CAS  PubMed  Google Scholar 

  • Yang CQ, Fang X, Wu XM, Mao YB, Wang LJ, Chen XY (2012) Transcriptional regulation of plant secondary metabolism F. J Integr Plant Biol 54:703–712

    Article  CAS  PubMed  Google Scholar 

  • Yazaki K (2005) Transporters of secondary metabolites. Curr Opin Plant Biol 8:301–307

    Article  CAS  PubMed  Google Scholar 

  • Yazaki K (2006) ABC transporters involved in the transport of plant secondary metabolites. FEBS Lett 580:1183–1191

    Article  CAS  PubMed  Google Scholar 

  • Yazaki K, Sugiyama A, Morita M, Shitan N (2008) Secondary transport as an efficient membrane transport mechanism for plant secondary metabolites. Phytochem Rev 7:513–524

    Article  CAS  Google Scholar 

  • Ye Y, Ding Y, Jiang Q, Wang F, Sun J, Zhu C (2017) The role of receptor-like protein kinases (RLKs) in abiotic stress response in plants. Plant Cell Rep 36:235–242

    Article  CAS  PubMed  Google Scholar 

  • Yi TG, Yeoung YR, Choi I-Y, Park N-I (2019) Transcriptome analysis of Asparagus officinalis reveals genes involved in the biosynthesis of rutin and protodioscin. PLoS ONE 14:e0219973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang B, Horvath S (2005) A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol 4:e17

  • Zhang X, Mi X, Chen C, Wang H, Guo W (2018) Identification on mitogen-activated protein kinase signaling cascades by integrating protein interaction with transcriptional profiling analysis in cotton. Sci Rep 8:1–14

    Google Scholar 

  • Zhao Q, Dixon RA (2011) Transcriptional networks for lignin biosynthesis: more complex than we thought? Trends Plant Sci 16:227–233

    Article  CAS  PubMed  Google Scholar 

  • Zheng Y, Jiao C, Sun H, Rosli HG, Pombo MA, Zhang P, Banf M, Dai X, Martin GB, Giovannoni JJ (2016) iTAK: a program for genome-wide prediction and classification of plant transcription factors, transcriptional regulators, and protein kinases. Mol Plant 9:1667–1670

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Ali Niazi.

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Bolhassani, M., Niazi, A., Tahmasebi, A. et al. Identification of key genes associated with secondary metabolites biosynthesis by system network analysis in Valeriana officinalis. J Plant Res 134, 625–639 (2021). https://doi.org/10.1007/s10265-021-01277-5

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