Response surface methodology (RSM) is a three factorial model which illustrates the relationship between one or more independent variables. RSM can be used to optimize the fermentation medium for the production of Cyclosporin A from the isolate Tolypocladium inflatum. The optimal point of the response surface area is predicted by using a seconddegree polynomial model and applying the statistic model obtained from the central composite design (CCD). The results of optimizing the fermentation medium for Cyclopsorin using the three independent variables of glucose, casein, and KH2PO4 show that all three of the independent variables affect the production of Cyclosporin A. There is a positive interaction between the independent variables of glucose and casein, however, there is no visible interaction between glucose with KH2PO4 and casein with KH2PO4. By using the mathematical model the total optimum result obtained is 1230.5 mg L-1, glucose concentrate 28.5 g L-1, KH2PO4 concentrate 0.74 gL-1, and casein concentrate 9.8 g L-1. Laboratory validation shows that Cyclosporin A productivity is 1197.285 mg L-1. There is a value difference of 2.7% between the expected productivity of Cyclosporin A using the mathematical model and the actual production in laboratory tests.

Bahasa Abstract

Optimasi Medium Fermentasi untuk Produksi Cyclosporin A Menggunakan Response Surface Methodology. Response surface methodology (RSM) merupakan model tiga faktorial yang dapat menjelaskan hubungan antar variabel independen satu sama lainnya. RSM dapat digunakan untuk optimasi medium fermentasi produksi Cyclosporin A menggunakan isolat Tolypocladium inflatum. Daerah permukaan respon yang merupakan titik optimum dapat diduga dengan menggunakan model polinomial orde kedua dengan menerapkan model statistik central composite design (CCD). Hasil optimasi medium fermentasi produksi Cyclopsorin A dengan menggunakan variabel bebas glukosa, kasein, dan KH2PO4 menunjukkan bahwa ketiga variabel bebas tersebut memiliki pengaruh nyata terhadap produktivitas Cyclosporin A. Ada interaksi positif diantara variabel bebas glukosa dengan kasein, namun demikian tidak terdapat interaksi nyata diantara glukosa dengan KH2PO4 dan kasein dengan KH2PO4. Dengan menggunakan model matematik diperoleh data titik optimum sebesar 1230.5 mg L-1 pada konsentrasi glukosa 28.5 g L-1, konsentasi KH2PO4 0.74 g L-1, dan konsentrasi kasein 9.8 g L-1. Hasil validasi data yang dilakukan dilaboratorium diperoleh produktivitas Cyclosporin A sebesar 1197.28 mg L-1. Dengan demikian terdapat perbedaan 2.7% antara produktivitas Cyclosporin A yang dihasilkan dari nilai dugaan menggunakan model matematik dengan nilai sebenarnya yang diperoleh dari hasil percobaan di laboratorium.


I.A. Sallam, A.M. El-Rifai, A.H. Hamdi, A. ElMinofi, Abd. Elsalam, J. Gen Applied Microbiol. 36 (2005) 231

R.M.P. Derks, S.M. Madris, Genet. Genomic 206 (2001) 527

H. Upton, Origin of Drugs in Current Use: The Cyclosporine Story. http://www.newscornell.edu/releases/2002/cyclosporine.html.2001.

J.F. Borel, Wien Klin Wochenschr, 114 (2002) 433.

M. Gharavi, R.B. Najafi, A. Kloobandi, Saudi Pharm. J. 2 (2004) 112.

T. Robinson, D. Singh, P. Nigam, Applied Microbiol Biotechnol. 55 (2001) 284.

S.N. Agathos, C. Madhosingh, J.W. Marshall, J. Lee, Ann. N.Y. Acad. Sci. 506 (1987) 657.

Y.R. Fattah, H.E. Enshasy, M. Anwar, H. Omar, E. Abolmagd, R.A. Zahra, J. Microbiol. Biotechnol. 17 (2007) 1930.

J. Lee, S.N. Agathos, Applied Microbiol Biotechnol. 34 (1991) 513.

A.K. Nisha, S. Meignanalakshmi, K. Ramasamy. Biotechnol. 7 (2008) 549.

R. Sunaryanto, Prosiding Seminar Nasional Tjipto Utomo, 4 (2005) A6-1.

C.C. Isaac, A. Jones, M.A. Pickard, Antimicrob. Agents Chemother. 34 (1990) 121.

D.C. Montgomery, Design And Analysis Of Experiments, 3th ed., John Wiley and Sons, New York, 1997, p.87.

M. Sallam, A.H. El-Rifai, A.H. El-Minofi, AbdElsalam, J. Gen Appl Microbiol 49 (2003) 321.

S.A. Survase, N.S. Shaligram. R.C. Pansuriya, U.S. Annpure, Biotechnol. Biopro. Eng. 19 (2009) 462.

H. Kobel, R. Traber, Appl Microbiol Biotechnol. 14 (1984) 237.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.