Browse > Article

Selective Production of Epothilone B by Heterologous Expression of Propionyl-CoA Synthetase in Sorangium cellulosum  

Han, Se-Jong (Department of Chemical Engineering, Sungkyunkwan University)
Park, Sang-Woo (Department of Chemical Engineering, Sungkyunkwan University)
Kim, Byung-Woo (Department of Chemical Engineering, Sungkyunkwan University)
Sim, Sang-Jun (Department of Chemical Engineering, Sungkyunkwan University)
Publication Information
Journal of Microbiology and Biotechnology / v.18, no.1, 2008 , pp. 135-137 More about this Journal
Abstract
The metabolic engineering of epothilones, as secondary metabolites, was investigated using Sorangium cellulosum to achieve the selective production of epothilone B, a potent anticancer agent. Thus, the propionyl-CoA synthetase gene (prpE) from Ralstonia solanacearum was heterologously expressed in S. cellulosum to increase the production of epothilone B. Propionyl-CoA synthetase converts propionate into propionyl-CoA, a potent precursor of epothilone B. The recombinant S. celluloslim containing the prpE gene exhibited a significant increase in the resolution of epothilones B/A, with an epothilone B to A ratio of 127 to 1, which was 100 times higher than that of the wild-type cells, demonstrating its potential use for the selective production of epothilone B.
Keywords
Epothilone; heterologous expression; metabolic engineering; propionyl-CoA synthetase; Sorangium cellulosum;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
Times Cited By Web Of Science : 3  (Related Records In Web of Science)
연도 인용수 순위
1 Park, S. W., S. H. Choi, Y. J. Yoon, D. H. Lee, D. J. Kim, J.-H. Kim, Y. K. Lee, G. J. Choi, I.-T. Yeom, and S. J. Sim. 2006. Enhanced production of epothilones by carbon sources in Sorangium cellulosum. J. Microbiol. Biotechnol. 16: 519-523   과학기술학회마을
2 Rudd, K. E. and D. R. Zusman. 1982. RNA polymerase of Myxococcus xanthus: Purification and selective transcription in vitro with bacteriophage templates. J. Bacteriol. 151: 89-105
3 Seo, M.-J., E.-M. Im, J.-Y. Nam, and S.-O. Kim. 2007. Increase of CoQ10 production level by the coexpression of decaprenyl diphosphate synthase and 1-deoxy-D-xylulose 5-phosphate synthase isolated from Rhizobium radiobacter ATCC 4718 in recombinant Escherichia coli. J. Microbiol. Biotechnol. 17: 1045-1048   과학기술학회마을
4 Molnár, I., T. Schupp, M. Ono, R. E. Zirkle, M. Milnamow, B. Nowak-Thompson, N. Engel, C. Toupet, A. Stratmann, D. D. Cyr, J. Gorlach, J. M. Mayo, A. Hu, S. Goff, J. Schmid, and J. M. Ligon. 2000. The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90. Chem. Biol. 7: 97-109   DOI   ScienceOn
5 Gerth, K., H. Steinmetz, G. Höfle, and H. Reichenbach. 2000. Studies on the biosynthesis of epothilones: The biosynthetic origin of the carbon skeleton. J. Antibiot. 53: 1373-1377   DOI   ScienceOn
6 Park, N.-S., H.-J. Park, K. Han, and E.-S. Kim. 2006. Heterologous expression of novel cytochrome P450 hydroxylase genes from Sebekia benihana. J. Microbiol. Biotechnol. 16: 295-298   과학기술학회마을
7 Park, S. W., S. J. Han, D.-S. Kim, and S. J. Sim. 2007. Improvement of epothilone B production by in situ removal of ammonium using cation exchange resin in Sorangium cellulosum culture. Biochem. Eng. J. 37: 328-331   DOI   ScienceOn
8 Frykman, S., H. Tsuruta, J. Lau, R. Regentin, S. Ou, C. Reeves, J. Carney, D. Santi, and P. Licari. 2002. Modulation of epothilone analog production through media design. J. Ind. Microbiol. Biotechnol. 28: 17-20   DOI
9 Gerth, K., H. Steinmetz, G. Höfle, and H. Reichenbach. 2001. Studies on the biosynthesis of epothilones: The PKS and epothilone C/D monoxygenase. J. Antibiot. 54: 144-148   DOI   ScienceOn
10 Gerth, K., N. Bedorf, G. Höfle, H. Irschik, and H. Reichenbach. 1996. Epothilones A and B: Antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria) production, physicochemical and biological properties. J. Antibiot. 49: 560-563   DOI
11 Chou, T. C., X. G. Zhang, A. Balog, D. S. Su, D. Meng, K. Savin, J. R. Bertino, and S. J. Danishefsky. 1998. Desoxyepothilone B: An efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B. Proc. Natl. Acad. Sci. USA 95: 9642-9647
12 Regentin, R., S. Frykman, J. Lau, H. Tsuruta, and P. Licari. 2003. Nutrient regulation of epothilone biosynthesis in heterologous and native production strains. Appl. Microbiol. Biotechnol. 61: 451-455   DOI
13 Bollag, D. M., P. A. McQueney, J. Zhu, O. Hensens, L. Koupal, J. Liesch, M. Goetz, E. Lazarides, and C. M. Woods. 1995. Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res. 55: 2325-2333
14 Park, S. W., S. J. Park, S. J. Han, J. Lee, D.-S. Kim, J.-H. Kim, B. W. Kim, J. Lee, and S. J. Sim. 2007. Repeated batch production of epothilone B by immobilized Sorangium cellulosum. J. Microbiol. Biotechnol. 17: 1208-1212   과학기술학회마을
15 Kowalski, R. J., P. Giannakakou, and E. Hamel. 1997. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel. J. Biol. Chem. 272: 2534-2541   DOI   ScienceOn
16 Rajashekhara, E. and K. Watanabe. 2004. Propionyl-coenzyme A synthetases of Ralstonia solanacearum and Salmonella choleraesuis display atypical kinetics. FEBS Lett. 556: 143-147   DOI
17 Tang, L., S. Shah, L. Chung, J. Carney, L. Katz, C. Khosla, and B. Julien. 2000. Cloning and heterologous expression of the epothilone gene cluster. Science 287: 640-642   DOI