Streptomyces peucetius subsp. caesius 돌연변이주에 의한 doxorubicin생산의 최적배양조건

김승욱; 송수문; 문순옥

Journal of the Korean Industrial and Engineering Chemistry, Vol.8, No.4, 660-666, August, 1997

Export Citation

Streptomyces peucetius subsp. caesius 돌연변이주에 의한 doxorubicin생산의 최적배양조건

Optimal Culture Conditions for Doxorubicin Production by a Mutant of Streptomyces peucetius subsp. caesius

김승욱, 송수문, 문순옥

초록

본 연구에서는 Streptomyces peucetius subsp. caesius 돌연변이주에 의한 doxorubicin의 생산에 있어서 배양조건 및 배지의 성분을 확립하여 doxorubicind의 생산을 높이는데 목적이 있다. Doxorubicin 생산을 위한 최적 배지조성은 4% maltose, 0.5% HEPES, 0.02% K₂HPO₄, 0.01% MgSO₄로 나타났고, 가장 적합한 종균 접종량과 시기는 10% (v/v), 72시간이었다. Doxorubicin생산에 적합한 소포제를 찾기위해 여러 종류의 소포제를 배지에 첨가한 결과 가장 적합한 소포제는 KG(10% K+ 10% G)이었으며 최적농도는 0.01%이었다. 교반식반응기에서 배양할 경우 적합한 통기량은 1.5v/v min으로 최대 29mg/1의 doxorubicin을 생산하였고, 1.0v/v nin의 경우에도 플라스크 배양보다 15% 증가된 23mg/1의 doxorubicin을 생산하였다.

The production of doxorubicin by a mutant of Streptomyces peucetius subsp. caesius was studied. The optimal culture conditions, such as inoculum size and medium composition were established to improve the productivity of doxorubicin. The optimal medium composition was found to be 4% maltose, 0.5% HEPES, 0.02% K₂HPO₄, 0.01% MgSO₄. As an antiform agent, 0.001% KG(10% Adekanol +10% Silicone) was suitable one among various agents. Culture was carried out in 2.5 L jar-fermenter with different aeration rates of 1.5, 1.0, and 1.5 v/v min. The maximum production of doxorubicin(29 mg/l) was obtained at 1.5 v/v min of aeration rate, and even at 1.0 v/v min, the production of doxorubicin was increased up to l5% compared with that of shake-flask culture.

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[2] Rhem HJ, Reed G, Biotechnology, 4, 512 (1986)

[3] Arcamone F, Cassinelli G, Frantini G, Grein A, Orezzi P, Pal C, Spall C, Biotechnol. Bioeng., 11, 1101 (1969)

[4] Bachur NR, Yu F, Johnson R, Wickey R, Wu Y, Markas L, Mol. Pharmacol., 41, 993 (1992)

[5] Yoshimoto A, Oki T, Umezawa H, J. Antibiot., 33, 1199 (1980)

[6] Oki T, Takatsuki Y, Tobe H, Yoshimoto A, Takeuchi T, Umezawa H, J. Antibiot., 34, 1229 (1981)

[7] Dekleva ML, Titus JA, Strohl WR, Can. J. Microbiol., 31, 287 (1985)

[8] Dekleva ML, Strobl WR, J. Can. Microbiol., 33, 1129 (1987)

[9] McGuire JC, Hamilton BK, White RJ, Process Biochem., 14, 2 (1979)

[10] Arcamone F, Medical Series, Academic Press, 1 (1981)

[11] Martin JF, Demain AL, Microbiol. Rev., 44, 230 (1988)

[12] Chater KF, Cold Spring Harbour Laboratory, New York, 89 (1984)

[13] Bulock J, Kristiansen B, Basic Biotechnol., 16, 421 (1987)

[14] Umezawa H, Kouno K, Ishihara T, Yoshimoto A, Takatsuki Y, Tobe H, U.S. Patent, 4,592,999 (1986)

[15] Lebrihi A, Germain P, Appl. Microbiol. Biotechnol., 26, 130 (1989)

[16] Pinnert S, PreudHomme J, U.S. Patent, 3,997,662 (1976)