Revealing The Motifs, Properties, and Phylogeny of Lupeol Synthase Using Bioinformatics Approach

Ika Qurrotul Afifah, Esti Wahyu Widowati

Abstract


Lupane-type triterpenoid saponins are potent plants’ secondary metabolites for drug development as they showed various activities such as anticancer, Sarcoplasmic Reticulum Ca2+-ATPase (SERCA) activator which is very important for neurons, and antileishmanial. The triterpenoid saponin backbone is produced by cyclization and rearrangement of the 2,3-oxidosqualene precursor by the oxidosqualene cyclase. The type of oxidosqualene cyclase involved determines the type of saponins so it is referred to as a key enzyme. Lupane-type saponins are produced by 2,3-oxidosqualene cyclization through the chair-chair-chair conformation and the formation of various cation intermediates. This study aimed to analyze lupeol synthase, the key enzyme which determines the conversion of 2,3-oxidosqualene into lupane-type saponins.  This in silico project was done using bioinformatics programs including Multiple Em for Motif Elicitation (MEME), ProtParam, and Molecular Evolutionary Genetic Analysis (MEGA-X) for relationship analysis. The amino acid sequences analysis using the MEME program showed that lupeol synthase has QW, DCTAE, and CYCR conserved motifs in the oxidosqualene cyclase family even though some evolutions were also present. Analysis of chemical and physical parameters with ProtParam indicated that lupeol synthase had lower stability than lanosterol synthase from Saccharomyces cerevisiae. The phylogenetic tree showed that lupeol synthase was closely related to other plant oxidosqualene cyclases. The results of this study are expected to support the modification strategy determination to increase the production of lupane-type saponins using a biotechnological approach in the pharmaceutical industry.


Keywords


Bioinformatics, lupeol synthase, lupane, motifs, saponins

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References


Augustin, J. M., Kuzina, V., Andersen, S. B., & Bak, S. (2011). Molecular activities, biosynthesis and evolution of triterpenoid saponins. In Phytochemistry. https://doi.org/10.1016/j.phytochem.2011.01.015

Bailey, T. L., & Elkan, C. (1994). Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proceedings / ... International Conference on Intelligent Systems for Molecular Biology ; ISMB. International Conference on Intelligent Systems for Molecular Biology.

Bailey, Timothy L., Johnson, J., Grant, C. E., & Noble, W. S. (2015). The MEME Suite. Nucleic Acids Research. https://doi.org/10.1093/nar/gkv416

Basyuni, M., & Wati, R. (2017). Bioinformatics analysis of the oxidosqualene cyclase gene and the amino acid sequence in mangrove plants. Journal of Physics: Conference Series. https://doi.org/10.1088/1742-6596/801/1/012011

Basyuni, M., Wati, R., Sulistiyono, N., Hayati, R., Sumardi, Oku, H., Baba, S., & Sagami, H. (2018). Protein modelling of triterpene synthase genes from mangrove plants using Phyre2 and Swiss-model. Journal of Physics: Conference Series. https://doi.org/10.1088/1742-6596/978/1/012095

Basyuni, Mohammad, Oku, H., Tsujimoto, E., Kinjo, K., Baba, S., & Takara, K. (2007). Triterpene synthases from the Okinawan mangrove tribe, Rhizophoraceae. FEBS Journal. https://doi.org/10.1111/j.1742-4658.2007.06025.x

Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S., Wilkins, M. R., Appel, R. D., & Bairoch, A. (2005). Protein Identification and Analysis Tools on the ExPASy Server. In The Proteomics Protocols Handbook. https://doi.org/10.1385/1-59259-890-0:571

Guhling, O., Hobl, B., Yeats, T., & Jetter, R. (2006). Cloning and characterization of a lupeol sintase involved in the synthesis of epicuticular wax crystals on stem and hypocotyl surfaces of Ricinus communis. Archives of Biochemistry and Biophysics. https://doi.org/10.1016/j.abb.2005.12.013

Haralampidis, K., Trojanowska, M., & Osbourn, A. E. (2002). Biosynthesis of triterpenoid saponins in plants. In Advances in biochemical engineering/biotechnology. https://doi.org/10.1007/3-540-44604-4_2

Hayashi, H., Huang, P., Takada, S., Obinata, M., Inoue, K., Shibuya, M., & Ebizuka, Y. (2004). Differential expression of three oxidosqualene cyclase mRNAs in Glycyrrhiza glabra. Biological and Pharmaceutical Bulletin. https://doi.org/10.1248/bpb.27.1086

Jia, H. M., Jia, H. J., Cai, Q. Le, Wang, Y., Zhao, H. B., Yang, W. F., Wang, G. Y., Li, Y. H., Zhan, D. L., Shen, Y. T., Niu, Q. F., Chang, L., Qiu, J., Zhao, L., Xie, H. B., Fu, W. Y., Jin, J., Li, X. W., Jiao, Y., … Gao, Z. S. (2019). The red bayberry genome and genetic basis of sex determination. Plant Biotechnology Journal. https://doi.org/10.1111/pbi.12985

Kumar, S., Stecher, G., Li, M., Knyaz, C., & Tamura, K. (2018). MEGA X: Molecular evolutionary genetics analysis across computing platforms. Molecular Biology and Evolution. https://doi.org/10.1093/molbev/msy096

Kushiro, T., & Ebizuka, Y. (2010). Triterpenes. In Comprehensive Natural Products II: Chemistry and Biology. https://doi.org/10.1016/b978-008045382-8.00007-1

Qiao, W., Zhou, Z., Liang, Q., Mosongo, I., Li, C., & Zhang, Y. (2019). Improving lupeol production in yeast by recruiting pathway genes from different organisms. Scientific Reports. https://doi.org/10.1038/s41598-019-39497-4

Sawai, S., Shindo, T., Sato, S., Kaneko, T., Tabata, S., Ayabe, S. I., & Aoki, T. (2006). Functional and structural analysis of genes encoding oxidosqualene cyclases of Lotus japonicus. Plant Science. https://doi.org/10.1016/j.plantsci.2005.08.027

Teles, C. B. G., Moreira-Dill, L. S., Silva, A. de A., Facundo, V. A., de Azevedo, W. F., da Silva, L. H. P., Motta, M. C. M., Stábeli, R. G., & Silva-Jardim, I. (2015). A lupane-triterpene isolated from Combretum leprosum Mart. fruit extracts that interferes with the intracellular development of Leishmania (L.) amazonensis in vitro. BMC Complementary and Alternative Medicine. https://doi.org/10.1186/s12906-015-0681-9

Wang, Z., Yeats, T., Han, H., & Jetter, R. (2010). Cloning and characterization of oxidosqualene cyclases from Kalanchoe daigremontiana: Enzymes catalyzing up to 10 rearrangement steps yielding friedelin and other triterpenoids. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M109.098871

Xiong, J. (2006). Essential bioinformatics. In Essential Bioinformatics. https://doi.org/10.1017/CBO9780511806087

Xue, Z., Duan, L., Liu, D., Guo, J., Ge, S., Dicks, J., Ómáille, P., Osbourn, A., & Qi, X. (2012). Divergent evolution of oxidosqualene cyclases in plants. New Phytologist. https://doi.org/10.1111/j.1469-8137.2011.03997.x

Yang, G., Wang, Y., Yu, Y., Zheng, J., Chen, J., Li, S., Chen, R., Zhang, C., Naman, C. B., Yu, D., & Cao, Z. (2019). Schekwanglupaside C, a new lupane saponin from Schefflera kwangsiensis, is a potent activator of sarcoplasmic reticulum Ca2+-ATPase. Fitoterapia. https://doi.org/10.1016/j.fitote.2019.04.005

Ye, Y., Zhang, T., Yuan, H., Li, D., Lou, H., & Fan, P. (2017). Mitochondria-Targeted Lupane Triterpenoid Derivatives and Their Selective Apoptosis-Inducing Anticancer Mechanisms. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.7b00679




DOI: https://doi.org/10.33387/tjp.v10i1.3018

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Copyright (c) 2021 Ika Qurrotul Afifah, Esti Wahyu Widowati

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