Current Trends in <strong>Biotechnology</strong> <strong>and</strong> <strong>Pharmacy</strong> Vol. 5 (3) 1325 -1337 July 2011, ISSN 0973-8916 (Print), 2230-7303 (Online) 1335 Fig. 6. Effect <strong>of</strong> metabolic precursors on cephamycin C production by N. lactamdurans NRRL 3802 in SmF Cephamycin C (mg/L) DCW (g/l) Fig. 7. Effect <strong>of</strong> inducer (1,3-diaminopropane) on cephamycin C production by N. lactamdurans NRRL 3802 in SmF Sequential optimization <strong>of</strong> cephamycin C
Current Trends in <strong>Biotechnology</strong> <strong>and</strong> <strong>Pharmacy</strong> Vol. 5 (3) 1325 -1337 July 2011, ISSN 0973-8916 (Print), 2230-7303 (Online) 1336 different concentrations were screened, <strong>and</strong> were found to increase the production <strong>of</strong> cephamycin C as compared to control (Fig. 6). The effect <strong>of</strong> inducer on cephamycin C production: Diamines are known to increase the production <strong>of</strong> cephamycin C (8,9). 1,3- Diaminopropane (a three carbon diamine) was used as an inducer for the production <strong>of</strong> cephamycin C. It was added at 0.4-1.6% v/v to the RSM optimized media supplemented with amino acids. Fig. 7 shows the effect <strong>of</strong> 1,3- diaminopropane on production <strong>of</strong> cephamycin C. The optimum production <strong>of</strong> cephamycin C obtained was 3973.20 ± 57.96 mg/l at 1.2% v/v <strong>of</strong> 1,3-diaminopropane. 1,3-Diaminopropane increases the enzyme levels <strong>of</strong> lysine-6- aminotransferase <strong>and</strong> P6C dehydrogenase (the first <strong>and</strong> second enzymes <strong>of</strong> the cephamycin biosynthetic pathway) responsible for the conversion <strong>of</strong> lysine to á-aminoadipic acid (a rate limiting step) at transcriptional level (9). Conclusion Glycerol <strong>and</strong> yeast extract were found to be suitable carbon <strong>and</strong> nitrogen source for the production <strong>of</strong> cephamycin C from N. lactamdurans NRRL 3802. Taguchi L 16 - orthogonal array design demonstrated the effect <strong>of</strong> Na 2 S 2 O 3 , yeast extract, K 2 HPO 4 <strong>and</strong> L- glutamic acid in the production medium to be significant. Further optimization <strong>of</strong> the medium using RSM showed complex interaction between them <strong>and</strong> also increased the production <strong>of</strong> cephamycin C to 3042.19 ± 62.36 mg/l. There was a 12.52 fold increase in production <strong>of</strong> cephamycin C after RSM <strong>and</strong> 16.35 fold increase after addition <strong>of</strong> metabolic precursors <strong>and</strong> inducer. References 1. Stapley, E.O., Jackson, M., Hern<strong>and</strong>ez, S., Zimmerman, S.B., Currie, S.A., Mochale, S., Mata, J.M., Woodruff, H.B. <strong>and</strong> Henlin, D. (1972). Cephamycins, a new family <strong>of</strong> â-lactam antibiotics. Antimicrobial Agents <strong>and</strong> Chemotherapy, 2: 122-131. 2. Nagarajan, R., Boeck, L.D., Gorman, M., Hamill, R.L., Higgens, C.E., Hoehn, M.M., Starck, W.M. <strong>and</strong> Whitney, J.G. (1971). â- Lactam antibiotics from Streptomyces. Journal <strong>of</strong> the American Chemical Society, 93: 2308–2310. 3. Kumar, P. <strong>and</strong> Satyanarayana, T. (2007). Optimization <strong>of</strong> culture variables for improving glucoamylase production by alginate entrapped Thermomucor indicaeseudaticae using statistical methods. Bioresource Technology, 98: 1252-1259. 4. Survase, S.A., Annapure, U.S. <strong>and</strong> Singhal, R.S. (2009). Statistical optimization for improved production <strong>of</strong> cyclosporin A in solid-state fermentation. Journal <strong>of</strong> Microbiology <strong>and</strong> <strong>Biotechnology</strong> 19: 1385- 1392. 5. Kirpekar, A.C., Kirwant, D.J. <strong>and</strong> Stieber, R.W. (1991). Effects <strong>of</strong> glutamate, glucose, phosphate, <strong>and</strong> alkali metal ions on cephamycin C production by Nocardia lactamdurans in defined media. <strong>Biotechnology</strong> <strong>and</strong> Bioengineering, 38: 1100-1109. 6. Inamine, E. <strong>and</strong> Birnbaum, J. (1973). Fermentation process. US patent 3,770,590. 7. Ginther, C.L. (1979). Sporulation <strong>and</strong> serine protease production by Streptomyces lactamdurans. Antimicrobial Agents <strong>and</strong> Chemotherapy, 15: 522–526. 8. Inamine, E. <strong>and</strong> Birnbaum, J. (1976). Fermentation <strong>of</strong> cephamycin C. US patent 3,977,942. Lalit D. Kagliwal et al
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