Improvement of microbial strain and fermentation process of rapamycin biosynthesis

The purpose of this investigation is to enhance the production of the immunosuppressant drug rapamycin by subjecting the strain CBS 773.23 to ultraviolet (UV) and N-methyl-N′-nitro-N-nitroso guanidine (NTG) mutations. Among all the mutants tested, MTCC 5681 (NRC-CM03/SH) obtained by NTG mutagenesis...

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Published in:Preparative biochemistry & biotechnology 2013-08, Vol.43 (6), p.539-550
Main Authors: Baby Rani, Polavarapu, Battula, Suneel Kumar, Rao, A. K. S. Bhujanga, Gunja, Madhavi, Narasu, Mangamoori Lakshmi
Format: Article
Language:English
Subjects:
actinomycetes
culture conditions
Drugs
Fermentation
Hydrogen-Ion Concentration
Immune system
immunosuppressant
Industrial Microbiology - methods
Mutagenesis
Mutagens - pharmacology
Mutation
Nitrogen - metabolism
Nitrosoguanidines - pharmacology
NTG mutagenesis
Plant propagation
rapamycin
Sirolimus - metabolism
Starch - metabolism
Streptomyces - drug effects
Streptomyces - genetics
Streptomyces - growth & development
Streptomyces - metabolism
Streptomyces - radiation effects
Streptomyces hygroscopicus
Temperature
Ultraviolet Rays
Yeasts
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Summary:The purpose of this investigation is to enhance the production of the immunosuppressant drug rapamycin by subjecting the strain CBS 773.23 to ultraviolet (UV) and N-methyl-N′-nitro-N-nitroso guanidine (NTG) mutations. Among all the mutants tested, MTCC 5681 (NRC-CM03/SH) obtained by NTG mutagenesis of strain CBS 773.72 showed the highest activity, 210 mg/L. The effect of different factors including medium composition, pH, temperature, and intensity of mixing on rapamycin production was studied. Based on the study, the optimal concentrations of soluble starch and dry yeast granules were found to be 50 g/L and 1.5 g/L, respectively. Furthermore, optimal values for pH, temperature, and shaking speed were found to be 6.0, 28°C, and 220 rpm, respectively. The production of rapamycin increased 1.6-fold, to 360 mg/L, in shake-flask culture using the optimal combination of factors observed compared with basal cultivation medium using MTCC 5681 mutant strain.
ISSN:1532-2297
1082-6068
1532-2297
DOI:10.1080/10826068.2012.759969