Perkembangan Bioteknologi dalam Produksi Kolkisin Farmasetis

Anggita Putri Unggaran, Tina Rostinawati

Abstrak


Kolkisin merupakan alkaloid utama yang terkandung dalam tanaman Colchicum autumnale dan Gloriosa superba L. Senyawa kolkisin memiliki beberapa khasiat terapeutik, di antaranya sebagai antimitotik, anti-inflamasi dan antifibrotil. Kebutuhan pasar yang tinggi akan suplai kolkisin mendorong berbagai penelitian untuk menemukan metode yang paling efisien guna meningkatkan produksi kolkisin. Budidaya konvensional tidak mampu mencukupi kebutuhan yang tinggi akan produk metabolit kolkisin, sementara sintesis kimia tidak dapat menjadi solusi yang tepat karena sulitnya mensintesis senyawa metabolit sekunder dengan struktur kimia yang kompleks. Solusi yang paling tepat untuk meningkatkan produksi kolkisin adalah kultur sel tanaman secara in vitro. Namun metode ini pun masih memiliki beberapa keterbatasan sehingga perlu dioptimalkan. Artikel ini meninjau delapan strategi untuk optimalisasi kultur sel, di antaranya elisitasi, product removal in situ, imobilisasi kultur sel tanaman, suspensi kultur sel tanaman dalam bioreaktor, demetilasi kolkisin dengan bantuan mikroba, mikrotuberisasi, kultur biorhizoma dengan bantuan enzim khusus, dan kultur biorhizoma dalam bioreaktor. Berdasarkan hasil tinjauan, dapat disimpulkan bahwa mikrotuberisasi, kultur biorhizoma dengan bantuan enzim khusus, dan kultur biorhizoma menggunakan bioreaktor merupakan strategi yang tengah banyak dikembangkan saat ini dan dinilai efisien untuk produksi kolkisin secara komersil.

Kata Kunci: kolkisin, kultur sel tanaman, biorhizoma, bioreaktor


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Referensi


Sivakumar, G. 2017. Upstream biomanufacturing of pharmaceutical colchicine. Critical Reviews in Biotechnology, DOI : 10.1080/07388551.2017.1312269.

Ade, R., dan Rai, M.K. 2010. Review: Colchicine, current advances and future prospects. Nusantara Bioscience, Vol. 2 (2) : 90-96.

Herdman, C. A., Strecker, T. E., Tanpure, R. P., Chen, Z., Winters, A., Gerberich, J., et al. 2016. Synthesis and biological evaluation of benzocyclooctene-based and indene-based anticancer agents that function as inhibitors of tubulin polymerization. Medchemcomm, 7 : 2418–2427.

Yokoyama, C., Yajima, C., Machida, T., Kawahito, Y., Uchida, M., dan Hisatomi, H. 2017. Interleukin-8 enhances the effect of colchicine on cell death. Biochem. Biophys. Res. Commun., 485 : 89–94.

Wilson, L., dan Saseen, J. J. 2016. Gouty arthritis: a review of acute management and prevention. Pharmacotherapy, 36 : 906–922.

Abhishek, A., Roddy, E., dan Doherty, M. 2017. Gout - a guide for the general and acute physicians. Clin. Med.,17 : 54–59.

Solak, Y., Siriopol, D., Yildiz, A., Yilmaz, M. I., Ortiz, A., Covic, A., et al. 2017. Colchicine in renal medicine: new virtues of an ancient friend. Blood Puri.f, 43 : 125–135.

Bourgaud, F.; Gravot, A.; Milesi, S.; Gontier, E. 2011. Production of plant secondary metabolites: a historical perspective. Plant Sci., 161 : 839–851.

Kolewe, M.E., Gaurav, V., dan Roberts, S.C. 2008. Pharmaceutically Active Natural Product Synthesis and Supply via Plant Cell Culture Technology. Molecular Pharmaceutics, 5 (2) : 243-256.

Sivakumar G. 2013. Colchicine semisynthetics: chemotherapeutics for cancer. Curr Med Chem., 20 : 892–898.

Wink, M., Alfermann, A. W., Franke, R.., Wetterauer, B., et al. 2005. Sustainable bioproduction of phytochemicals by plant in vitro cultures: anticancer agents. Plant Genet. Resources, 3 : 90–100.

Pitta-Alvarez, S.I., Spollansky, T.C., dan Giulietti, A.M. 2000. The influence of different biotic and abiotic elicitors on the production and profile of tropane alkaloids in hairy root cultures of Brugmansia candida. Enzyme Microb. Technol., 26 : 252–258.

Zambre, M., B. Chowdhury, Y. H. Kuo, M. V. Montagu, G. Angenon and F. Lambein. 2002. Prolific regeneration of fertile plants from green nodular callus induced from meristematic tissues in Lathyrus sativus L. (grass pea). Plant Sci., 163 : 1107-1112.

Zhang, K. R., dan John, P. C. L. 2005. Raised level of cyclin dependent kinase A after prolonged suspension culture of Nicotiana plumbaginifolia is associated with more rapid growth and division, diminished cytoskeleton and lost capacity for regeneration: implications for instability of cultured plant cells. Plant Cell Tissue Organ Cult., 82 : 295–308.

Dubey, K.K., Ray, A.R., dan Behera, B.K. 2008. Production of demethylated colchicine through microbial transformation and scale-up process development. Process Biochemistry, 43 : 251–257.

Sivakumar, G., Yu, K.W., Lee, J.S. 2006. Tissue cultured mountain ginseng adventitious rootsTM : safety and toxicity evaluation. Eng Life Sci., 6 : 372–383.

Sivakumar, G., Medina-Bolivar, F., Lay, J.O., et al. 2011. Bioprocess and bioreactor: next generation technology for production of potential plant-based antidiabetic and antioxidant molecules. Curr Med Chem., 18 : 79–90.

Mukhopadhyay, M.J., Lahiri, K., dan Mukhopadhyay, S. 2008. In vitro Microtuberization and Enhanced Colchicine Accumulation in Two Species of Gloriosa. Cytologia, 73 (4) : 357–363.

Al-Sane , K.O., et al. 2005. Cell suspension culture and secondary metabolites production in african violet (Saintpaulia ionantha Wendl). Jordan Journal of Agricultural Sciences, 1 (1) : 84-92.

Wang, Y. D., Yuan, Y. J., dan Wu, J. C. 2004. Induction studies of methyl jasmonate and salicylic acid on taxane production in suspension cultures of Taxus chinensis var. mairei. Biochem. Eng. J., 19 : 259–265.

Chen, H., Chen, F., Chiu, Francis ,C.K., dan Lo Cindy, M.Y. 2001. The effect of yeast elicitor on the growth and secondary metabolism of hairy root cultures of Salvia miltiorrhiza. Enzyme Microb. Technol., 28 : 100–105.

Ghosh, B., Mukherjee, M., Jha, T.B., dan Jha, S. 2002. Enhanced colchicine production in root cultures of Gloriosa superba by direct and indirect precursors of the biosynthetic pathway. Biotechnol. Lett., 24 : 231–234.

Ghosh, S., Ghosh, B., dan Jha, S. 2006. Aluminium chloride enhances colchicine production in root cultures of Gloriosa superba. Biotechnology Letters, 28 : 497–503.

Doran, P. M. 2006. Foreign protein degradation and instability in plants and plant tissue cultures. Trends Biotechnol., 24 : 426–432.

Verpoorte, R., Contin, A., Memelink, J. 2002. Biotechnology for the production of plant secondary metabolites. Phytochem. ReV, 1 : 13–25.

Bourgaud, F., Gravot, A., Milesi, S., dan Gontier, E. 2001. Production of plant secondary metabolites: a historical perspective. Plant Sci., 161 : 839–851.

Zhong, J. 2002. Biochemical engineering of the production of plant specific secondary metabolies by cell suspension cultures. AdV. Biochem. Eng. Biotechnol., 72 : 2–26.

Boye, O., dan Brossi, A. 1992. Tropolonic Colchicine Alkaloids and Allocongeners. Dalam : Brossi, A., Cordell, G., editors. The Alkaloids Chemistry and Pharmacology, Vol. 41. New York and London : Academic Press.

Poulev, A., Bombardelli, E., Ponzone, C., Zenk, M.H. 1995. Regioselective bioconversion of colchicine and thiocolchicine into their corresponding 3- demethyl derivatives. J Ferment Bioeng., 79 : 33–38.

Solet J,M., Bister, Miel, F., Galons, H., Spagnoli, R., Guignard, J.L., Cosson, L. 1993. Glycosylation of thiocholchicine by a cell suspension culture of Centella asiatica Phytochemistry, Vol. 33. Oxford, New York : Pergamon Press.

Huang, Q., Huang, X., Deng, J., et al. 2016. Differential gene expression between leaf and rhizome in Atractylodes lancea: a comparative transcriptome analysis. Front Plant Sci., 7 : 348.

Sivakumar, G., Yu, K.W., Paek, K.Y. 2005. Production of biomass and ginsenosides from adventitious roots of Panax ginseng in bioreactor cultures. Eng Life Sci., 5 : 333–342.

Murashige, T., Skoog, F. 1962. A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol Plant, 15 : 473-497.

Sivakumar, G., Yu, K.W., Lee, J.S. 2006. Tissue cultured mountain ginseng adventitious rootsTM : safety and toxicity evaluation. Eng Life Sci., 6 : 372–383.

Bhatia, S., dan Bera, T. 2015. Chapter 7 - Classical and Nonclassical Techniques for Secondary Metabolite Production in Plant Cell Culture. Modern Applications of Plant Biotechnology in Pharmaceutical Sciences : 231-291. DOI : 10.1016/B978-0-12-802221-4.00007-8.




DOI: https://doi.org/10.24198/jf.v16i3.17577

DOI (PDF): https://doi.org/10.24198/jf.v16i3.17577.g8977

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