Sains Malaysiana 47(12)(2018): 2985–2992

http://dx.doi.org/10.17576/jsm-2018-4712-07

 

Reconstruction of Curcuma aeruginosa Secondary Metabolite Biosynthetic Pathway using Omics Data

(Pembinaan Semula Tapak Jalan Biosintetik Metabolit Sekunder Curcuma aeruginosa Menggunakan Data Omiks)

NURUL-SYAFIKA MOHAMAD-FAUZI¹, RABIATUL-ADAWIAH ZAINAL-ABIDIN², MOHD WAZNUL ADLY ZAIDAN³, SANIMAH SIMOH³, ALIZAH ZAINAL³ & ZETI-AZURA MOHAMED-HUSSEIN^1,2*

 

¹Centre for Frontier Sciences, Faculty of Science and Technology, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

 

²Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

 

³Institut Penyelidikan dan Kemajuan Pertanian Malaysia (MARDI), 43300 Serdang, Selangor Selangor Darul Ehsan, Malaysia

 

Diserahkan: 5 September 2018/Diterima: 19 September 2018

 

ABSTRACT

Curcuma aeruginosa or temu hitam is herbaceous plant with high therapeutic values in its rhizome that is widely used in traditional medicine. However, molecular studies on the secondary metabolite biosynthetic pathway of C. aeruginosa is still limited. Hence, the aim of this study was to explore and reconstruct the secondary metabolite biosynthetic pathway of C. aeruginosa rhizome by integrating the metabolite profiling and transcriptomic data. A total of 81 metabolites were identified in the rhizome of C. aeruginosa; amongst others are curzerene and β-Cubebene which are potent antioxidants. A total of 28,225 unigene were obtained from transcriptomic sequencing of C. aeruginosa rhizome and analysed to identify potential genes associated with the biosynthesis of its metabolites. Of these, 43 unigenes were identified and mapped onto five sub-pathways; i.e. carotenoid biosynthetic pathway, diterpenoid biosynthetic pathway, monoterpenoid biosynthetic pathway, terpenoid and steroid biosynthetic pathway, and sesquiterpenoid and triterpenoid biosynthetic pathway. This study demonstrated a systematic bioinformatic approach to reconstruct a metabolic pathway in the rhizome of C. aeruginosa using bioinformatic approach.

 

Keywords: Data integration; metabolic pathway; metabolomics; pathway reconstruction; transcriptomic

 

ABSTRAK

Curcuma aeruginosa atau temu hitam merupakan sejenis tumbuhan herba yang mempunyai nilai terapeutik tinggi pada bahagian rizomnya dan telah digunakan secara meluas dalam perubatan tradisi. Namun begitu, masih banyak yang belum diketahui tentang penghasilan metabolit sekunder di dalam C. aeruginosa. Kajian ini dijalankan untuk membina semula tapak jalan biosintesis C. aeruginosa dengan menggunakan data pemprofilan metabolit sekunder dan transkriptomik. Sebanyak 81 metabolit telah dikenal pasti di dalam rizom seperti curzerene dan β-Cubebene yang berfungsi sebagai anti-oksidan. Sejumlah 28,225 unigen yang terhasil daripada penjujukan transkriptomik rizom C. aeruginosa telah dianalisis untuk mencari dan mengenal pasti sebarang gen yang terlibat di dalam penghasilan metabolit di dalam rizom C. aeruginosa. Terdapat 43 unigen telah dikenal pasti terlibat di dalam lima tapak jalan biosintetik utama iaitu biosintesis karotenoid, biosintesis diterpenoid, biosintesis monoterpenoid, biosintesis terpenoid dan steroid serta biosintesis sesquiterpenoid dan triterpenoid. Kajian ini juga memfokuskan kepada strategi pembinaan semula tapak jalan biosintetik yang terlibat dalam rizom C. aeruginosa dengan menggunakan pendekatan bioinformatik.

 

Kata kunci: Integrasi data; metabolomik; pembinaan semula tapak jalan; tapak jalan metabolik; transkriptomik

RUJUKAN

Abe, I., Rohmer, M. & Prestwich, G.D. 1993. Enzymatic cyclization of squalene and oxidosqualene to sterols and triterpenes. Chemical Reviews 93(6): 2189-2206.

Bateman, A., Martin, M.J., O’Donovan, C., Magrane, M., Apweiler, R., Alpi, E., Antunes, R., Arganiska, J., Bely, B., Bingley, M., Bonilla, C., Britto, R., Bursteinas, B., Chavali, G., Cibrian-Uhalte, E., Da Silva, A., De Giorgi, M., Dogan, T., Fazzini, F., Gane, P., Castro, L.G., Garmiri, P., Hatton- Ellis, E., Hieta, R., Huntley, R., Legge, D., Liu, W., Luo, J., Macdougall, A., Mutowo, P., Nightingale, A., Orchard, S., Pichler, K., Poggioli, D., Pundir, S., Pureza, L., Qi, G., Rosanoff, S., Saidi, R., Sawford, T., Shypitsyna, A., Turner, E., Volynkin, V., Wardell, T., Watkins, X., Zellner, H., Cowley, A., Figueira, L., Li, W., McWilliam, H., Lopez, R., Xenarios, I., Bougueleret, L., Bridge, A., Poux, S., Redaschi, N., Aimo, L., Argoud-Puy, G., Auchincloss, A., Axelsen, K., Bansal, P., Baratin, D., Blatter, M.C., Boeckmann, B., Bolleman, J., Boutet, E., Breuza, L., Casal-Casas, C., De Castro, E., Coudert, E., Cuche, B., Doche, M., Dornevil, D., Duvaud, S., Estreicher, A., Famiglietti, L., Feuermann, M., Gasteiger, E., Gehant, S., Gerritsen, V., Gos, A., Gruaz-Gumowski, N., Hinz, U., Hulo, C., Jungo, F., Keller, G., Lara, V., Lemercier, P., Lieberherr, D., Lombardot, T., Martin, X., Masson, P., Morgat, A., Neto, T., Nouspikel, N., Paesano, S., Pedruzzi, I., Pilbout, S., Pozzato, M., Pruess, M., Rivoire, C., Roechert, B., Schneider, M., Sigrist, C., Sonesson, K., Staehli, S., Stutz, A., Sundaram, S., Tognolli, M., Verbregue, L., Veuthey, A.L., Wu, C.H., Arighi, C.N., Arminski, L., Chen, C., Chen, Y., Garavelli, J.S., Huang, H., Laiho, K., McGarvey, P., Natale, D.A., Suzek, B.E., Vinayaka, C.R., Wang, Q., Wang, Y., Yeh, L.S., Yerramalla, M.S. & Zhang, J. 2015. UniProt: A hub for protein information. Nucleic Acids Research 43: 204-212.

Berardini, T.Z., Reiser, L., Li, D., Mezheritsky, Y., Muller, R., Strait, E. & Huala, E. 2015. The arabidopsis information resource: Making and mining the “gold standard” annotated reference plant genome. Genesis 53(8): 474-485.

Cameron, S.I., Smith, R.F. & Kierstead, K.E. 2005. Linking medicinal/nutraceutical products research with commercialization. Pharmaceutical Biology 43(5): 425-433.

Cavill, R., Jennen, D., Kleinjans, J. & Briedé, J.J. 2015. Transcriptomic and metabolomic data integration. Briefings in Bioinformatics 17(5): 891-901.

Chatr-Aryamontri, A., Oughtred, R., Boucher, L., Rust, J., Chang, C., Kolas, N.K., O’Donnell, L., Oster, S., Theesfeld, C., Sellam, A., Stark, C., Breitkreutz, B.J., Dolinski, K. & Tyers, M. 2017. The BioGRID interaction database: 2017 update. Nucleic Acids Research 45: 369-379.

Filippis, L.F.D. 2016. Plant secondary metabolites: From molecular biology to health products. In Plant-Environment Interaction: Responses and Approaches to Mitigate Stress, edited by Azooz, M.M. & Ahmad, P. New Jersey: Wiley- Blackwell. pp. 263-300.

Francke, C., Siezen, R.J. & Teusink, B. 2005. Reconstructing the metabolic network of a bacterium from its genome. Trends in Microbiology 13(11): 550-558.

Hastings, J., De Matos, P., Dekker, A., Ennis, M., Harsha, B., Kale, N., Muthukrishnan, V., Owen, G., Turner, S., Williams, M. & Steinbeck, C. 2013. The ChEBI reference database and ontology for biologically relevant chemistry: Enhancements for 2013. Nucleic Acids Research 41: 456-463.

Kamazeri, T.S.A.T., Samah, O.A., Taher, M., Susanti, D. & Qaralleh, H. 2012. Antimicrobial activity and essential oils of Curcuma aeruginosa, Curcuma mangga and Zingiber cassumunar from Malaysia. Asian Pacific Journal of Tropical Medicine 5(3): 202-209.

Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. 2016. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Research 44: 457-462.

de Las Rivas, J. & Fontanillo, C. 2010. Protein-protein interactions essentials: Key concepts to building and analyzing interactome networks. PLoS Computational Biology 6(6): 1-8.

de Oliveira Dal’Molin, C.G., Orellana, C., Gebbie, L., Steen, J., Hodson, M.P., Chrysanthopoulos, P., Plan, M.R., McQualter, R., Palfreyman, R.W. & Nielsen, L.K. 2016. Metabolic reconstruction of Setaria italica: A systems biology approach for integrating tissue-specific omics and pathway analysis of bioenergy grasses. Frontiers in Plant Science 7: 1-18.

Kitano, H. 2002. Computational systems biology. Nature 420: 206-210.

Lee, M.H., Jeong, J.H., Seo, J.W., Shin, C.G., Kim, Y.S., In, J.G., Yang, D.C., Yi, J.S. & Choi, Y.E. 2004. Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene. Plant and Cell Physiology 45(8): 976-984.

Li, S., Li, Y. & Smolke, C.D. 2018. Strategies for microbial synthesis of high-value phytochemicals. Nature Chemistry 10(4): 395-404.

Liu, Y., Roy, S.S., Nebie, R.H.C., Zhang, Y. & Nair, M.G. 2013. Functional food quality of Curcuma caesia, Curcuma zedoaria and Curcuma aeruginosa endemic to Northeastern India. Plant Foods for Human Nutrition 68: 72-77.

Matsuba, Y., Zi, J., Jones, A.D., Peters, R.J. & Pichersky, E. 2015. Biosynthesis of the diterpenoid lycosantalonol via nerylneryl diphosphate in Solanum lycopersicum. PLoS ONE 10(3): 1-16.

Othman, R., Mohd Zaifuddin, F.A. & Hassan, N.M. 2014. Carotenoid biosynthesis regulatory mechanisms in plants. Journal of Oleo Science 63(8): 753-760.

Rajkumari, S. & Sanatombi, K. 2018. Nutritional value, phytochemical composition, and biological activities of edible Curcuma species: A review. International Journal of Food Properties 20(3): 2668-2687.

Saithong, T., Rongsirikul, O., Kalapanulak, S., Chiewchankaset, P., Siriwat, W., Netrphan, S., Suksangpanomrung, M., Meechai, A. & Cheevadhanarak, S. 2013. Starch biosynthesis in cassava: A genome-based pathway reconstruction and its exploitation in data integration. BMC Systems Biology 7: 1-18.

Sanchez, S. & Demain, A.L. 2008. Metabolic regulation and overproduction of primary metabolites. Microbial Biotechnology 1(4): 283-319.

Sawai, S. & Saito, K. 2011. Triterpenoid biosynthesis and engineering in plants. Frontiers in Plant Science 2: 1-8.

Schläpfer, P., Zhang, P., Wang, C., Kim, T., Banf, M., Chae, L., Dreher, K., Chavali, A.K., Nilo-Poyanco, R., Bernard, T., Kahn, D. & Rhee, S.Y. 2017. Genome-wide prediction of metabolic enzymes, pathways, and gene clusters in plants. Plant Physiology 173(4): 2041-2059.

Seaver, S.M.D., Henry, C.S. & Hanson, A.D. 2012. Frontiers in metabolic reconstruction and modeling of plant genomes. Journal of Experimental Botany 63(6): 2247-2258.

Simoh, S. & Zainal, A. 2015. Chemical profiling of Curcuma aeruginosa Roxb. rhizome using different techniques of solvent extraction. Asian Pacific Journal of Tropical Biomedicine 5(5): 412-417.

Singh, B. & Sharma, R.A. 2015. Plant terpenes: Defense responses, phylogenetic analysis, regulation and clinical applications. 3 Biotech 5: 129-151.

Szklarczyk, D., Morris, J.H., Cook, H., Kuhn, M., Wyder, S., Simonovic, M., Santos, A., Doncheva, N.T., Roth, A., Bork, P., Jensen, L.J. & Von Mering, C. 2017. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Research 45: 362-368.

Vishwakarma, R.K., Patel, K., Sonawane, P., Kumari, U., Singh, S., Ruby, Abbassi, S., Agrawal, D.C., Tsay, H.S. & Khan, B.M. 2015. Squalene synthase gene from medicinal herb Bacopa monniera: Molecular characterization, differential expression, comparative modeling and docking studies. Plant Molecular Biology Reporter 33(6): 1675-1685.

Wurtele, E.S., Chappell, J., Daniel Jones, A., Celiz, M.D., Ransom, N., Hur, M., Rizshsky, L., Crispin, M., Dixon, P., Liu, J., Widrlechner, M.P. & Nikolau, B.J. 2012. Medicinal plants: A public resource for metabolomics and hypothesis development. Metabolites 2(4): 1032-1059.

Zaidan, M.W.A., Zainal, A., Jaganath, I.B. & Simoh, S. 2016. Transcriptomics and metabolomics data integration for identification the metabolic pathways in Curcuma aeruginosa. Proceedings of the International Conference on Natural Products 2016. Terengganu. p. 1.

 

*Pengarang untuk surat-menyurat; email: zeti.hussein@ukm.edu.my