Abstract
The immunosuppressant tacrolimus produced by Streptomyces sp. TST10 was purified in a process that included extraction, pre-adsorption using HP20 resin, adsorption using CG161M resin, and crystallization. In this study, the purification process using the adsorption resin CG161M was optimized by correlating tacrolimus yield with analogue load. One-step adsorption and two-step adsorption using CG161M can be applied selectively to the purification process, according to the analogue load of the input solution. We determined a correlation between the analogue load and the first adsorption yield in the two-step adsorption. We also observed yields according to the analogue loads in the one-step adsorption and the second adsorption of the two-step adsorption. As a result, the purification yields can be predicted by input conditions (analogue load). The purification strategy can be modified to achieve specific goals of purity, yield, and cost.
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Kino, T., H. Hatanaka, M. Hashimoto, M. Nishiyama, T. Goto, M. Okuhara, M. Kohsaka, H. Aoki, and H. Imanaka (1987) FK-506, a novel immunosuppressant isolated from a Streptomyces: I. Fermentation, isolation, and physico-chemical and biological characteristics. J. Antibiotics 40: 1249–1255.
Kino, T., H. Hatanaka, S. Miyata, N. Imaura, M. Nishiyama, T. Yakima, T. Goto, M. Okuhara, M. Kohsaka, H. Aoki, and T. Ochiai (1987) FK-506, a novel immunosuppressant isolated from a Streptomyces: II. Immunosuppressive effect of FK-506 in vitro. J. Antibiotics 40: 1256–1265.
Med Ad News (2010) Top 200 prescription medicines by sales. Med. Ad News 29(7): 10–15.
Kim, H. and Y. Park (2008) Isolation and identification of a novel microorganism producing the immunosuppressant Tacrolimus. J. Biosci. Bioeng. 105: 418–421.
Vaid, S. and P. Narula (2006) Novel process for producing Tacrolimus (FK-506) using vegetable oil as sole source of carbon. PCT, WO 2006/011156 A2.
Jung, S., S. Moon, K. Lee, Y. Park, S. Yoon, and Y. J. Yoo (2009) Strain development of Streptomyces sp. for tacrolimus production using sequential adaptation. J. Ind. Microbiol. Biotechnol. 36: 1467–1471.
Mollison, K. W., J. M. Andrews, T. A. Fey, L. N. Miller, R. A. Krause, P. T. Bretheim, and J. A. Brandt (1996) Discovery of FK 506 analogues that are nontoxic to mouse pancreatic beta cells in vitro but show diabetogenic potential when administered to the rat. Transplant. Proc. 28: 3185–3188.
Gregory, M. A. and C. J. Martin (2005) Production of polyketides and other natural products. US Patent 7,803,808 B2.
Or, Y. S., R. F. Clark, Q. Xie, J. McAlpine, D. N. Wittern., R. Henry, and J. R. Luly (1993) The chemistry of ascomycin: Structure determination and synthesis of pyrazole analogues. Tetrahedron 49: 8771–8786.
Cabri, W., P. Paissoni, J. Roletto, and L. Morra (2005) Process for the purification of tacrolimus. PCT. WO 2006/048145 A1.
Cvak, L., A. Jegorov, M. Buchta, P. Blantny, and J. Satke (2005) Process for isolation of crystalline tacrolimus. PCT, WO 2006/031664 A1.
Keri, V., A. Csorvasi, I. Melczer, and A. Simon (2005) Method of purifying tacrolimus. PCT, WO 2006/069386 A1.
Choi, B., Y. Ham, S. Yoo, K. Jung, and B. Kim (2008) Method for refining of high purity of Tacrolimus. KR Patent 2008-0024207.
http://www.dow.com/products/product_detail.page?product=1121040 (2011).
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Jung, S., Lee, K., Park, YJ. et al. Process development for purifying tacrolimus from Streptomyces sp. using adsorption. Biotechnol Bioproc E 16, 1208–1213 (2011). https://doi.org/10.1007/s12257-011-0128-1
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DOI: https://doi.org/10.1007/s12257-011-0128-1