Abstract
Clavulanic acid (CA) is a β-lactam antibiotic, which has a potent β-lactamase inhibiting activity. The influence of five variables, namely pH (6.0, 6.4, and 6.8), temperature (28°C, 30°C, and 32°C), agitation intensity (150, 200, and 250 rpm), glycerol concentration (5.0, 7.5, and 10 g/L) and soybean flour concentration (5.0, 12.5, and 20 g/L), on CA production by a new isolate of Streptomyces (DAUFPE 3060) was investigated in 250-mL Erlenmeyer flasks using a fractional factorial design. Temperature and soybean flour concentration were shown to be the two variables that exerted the most important effects on the production of CA at 95% confidence level. The highest CA concentration (494 mg/L) was obtained after 48 h at 150 rpm, 32°C, pH 6.0, 5.0 g/L glycerol, and 20 g/L soybean flour concentrations. Under these conditions, the yields of biomass and product on consumed substrate were 0.26 gX/gS and 64.3 mgP/gS, respectively. Fermentations performed in 3.0-L bench-scale fermenter allowed increasing the CA production by about 60%.
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Sánchez, S., & Olison, B. (2005). Current Opinion in Microbiology, 8, 229–233. doi:10.1016/j.mib.2005.04.016.
Elander, R. P. (2003). Applied Microbiology and Biotechnology, 61, 385–392.
Haginaka, J., Nakagawa, T., & Uno, T. (1981). Chemical & Pharmaceutical Bulletin, 29, 3334–3341.
Baggaley, K. H., Brown, A. G., & Schofield, C. J. (1997). Natural Product Reports, 14, 309–333. doi:10.1039/np9971400309.
Watve, M. G., Shejval, V., Sonawane, C., Rahalkar, M., Matapurkar, M., Shouche, Y., et al. (2000). Current Science, 78, 1535–1542.
Watve, M. G., Tickoo, R., Jog, M. M., & Bhole, B. D. (2001). Archives of Microbiology, 176, 386–390. doi:10.1007/s002030100345.
Gouveia, E. R., Baptista-Neto, A., Badino-Jr, A. C., & Hooka, C. O. (2001). Biotechnology Letters, 23, 157–161. doi:10.1023/A:1010356231673.
Chen, K. C., Lin, Y. H., Tsai, C. M., Hsieh, C. H., & Houng, J. Y. (2002). Biotechnology Letters, 24, 455–458. doi:10.1023/A:1014553109425.
Kirk, S., Avignone-Rossa, C. A., & Bushell, M. E. (2000). Biotechnology Letters, 22, 1803–1809. doi:10.1023/A:1005670603596.
Ortiz, S. C. A., Hokka, C. O., & Badino-Jr, A. C. (2007). Enzyme and Microbial Technology, 40, 1071–1077. doi:10.1016/j.enzmictec.2006.08.009.
Bruns, R. E., Scarminio, I. S., & Barros-Neto, B. (2006). Statistical design—Chemometrics. Amsterdam, Netherlands: Elsevier.
Saudagar, P. S., & Singhal, R. S. (2007). Applied Biochemistry and Biotechnology, 136, 345–359. doi:10.1007/s12010-007-9030-x.
Bersanetti, P. A., Almeida, R. M. R. G., Barboza, M. M. L., Araújo, G. C., & Hokka, C. O. (2005). Biochemical Engineering Journal, 23, 31–36. doi:10.1016/j.bej.2004.10.007.
Rosa, J. C., Neto, A. B., Hokka, C. O., & Badino, A. C. (2005). Bioprocess and Biosystems Engineering, 27, 99–104. doi:10.1007/s00449-004-0386-9.
Sircar, A., Sridhar, P., & Das, P. K. (1998). Process Biochemistry, 33, 283–289. doi:10.1016/S0032-9592(97)00058-7.
Lee, S. D., Park, S. W., Oh, K. K., Hong, S. I., & Kim, S. W. (2002). Letters in Applied Microbiology, 34, 370–375. doi:10.1046/j.1472-765X.2002.01102.x.
Kim, I. C., Kim, C. H., Hong, S. I., & Kim, S. W. (2001). World Journal of Microbiology & Biotechnology, 17, 869–872. doi:10.1023/A:1013895617923.
Wang, Y. H., Yang, B., Ren, J., Dong, M. L., Liang, D., & Xu, A. L. (2005). Process Biochemistry, 40, 1161–1166. doi:10.1016/j.procbio.2004.04.010.
Lawrence, C. H. (1956). Canadian Journal of Botany, 34, 44–47. doi:10.1139/b56-005.
Maranesi, G. L., Baptista-Neto, A., Hokka, C. O., & Badino-Jr, A. C. (2005). World Journal of Microbiology & Biotechnology, 21, 509–514. doi:10.1007/s11274-004-2393-z.
Bird, A. E., Bellis, J. M., & Gasson, B. C. (1982). Analyst (London), 107, 1241–1245. doi:10.1039/an9820701241.
Hae Bok, S., & Demain, A. L. (1977). Analytical Biochemistry, 81, 18–20. doi:10.1016/0003-2697(77)90593-0.
Teodoro, J. C., Baptista-Neto, A., Cruz-Hernández, I. L., Hokka, C. O., & Badino-Jr, A. C. (2006). Applied Microbiology and Biotechnology, 72, 450–455. doi:10.1007/s00253-005-0273-6.
Bushell, M. E., Kirk, S., Zhao, H. J., & Avignone-Rossa, C. A. (2006). Enzyme and Microbial Technology, 39, 149–157. doi:10.1016/j.enzmictec.2006.01.017.
Lynch, H. C., & Yang, Y. (2004). Enzyme and Microbial Technology, 34, 48–54. doi:10.1016/j.enzmictec.2003.08.003.
Roubos, J. A., Krabben, P., de Wtam, L., Babuska, R., & Heijen, J. J. (2002). Biotechnology Progress, 18, 451–457. doi:10.1021/bp020294n.
Mayer, A. F., & Deckwer, W. D. (1996). Applied Microbiology and Biotechnology, 45, 41–46. doi:10.1007/s002530050646.
Kenji, I., Viet Hung, T., Chan Lee, H., Liou, K., Shin, C. H., Yoon, Y. J., et al. (2006). Journal of Microbiology and Biotechnology, 16, 590–596.
Romero, J., Liras, P., & Martin, J. F. (1984). Applied Microbiology and Biotechnology, 20, 318–325. doi:10.1007/BF00270593.
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The authors gratefully acknowledge the financial support of the Brazilian Research Funding Institution FAPESP (process no. 05/60158-0).
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Viana, D.A., Carneiro-Cunha, M.N., Araújo, J.M. et al. Screening of Variables Influencing the Clavulanic Acid Production by Streptomyces DAUFPE 3060 Strain. Appl Biochem Biotechnol 160, 1797–1807 (2010). https://doi.org/10.1007/s12010-009-8671-3
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DOI: https://doi.org/10.1007/s12010-009-8671-3