Optimization of Streptomyces peucetius var. caesius N47 cultivation and epsilon-rhodomycinone production using experimental designs and response surface methods. 2004

K Kiviharju, and M Leisola, and T Eerikäinen
Laboratory of Bioprocess Engineering, Helsinki University of Technology, PL 6100, 02015 Hut, Finland. kristiina.kiviharju@hut.fi

Streptomyces peucetius var. caesius is an aerobic bacterium that produces doxorubicin as a secondary metabolite. A mixture design was applied for the screening of suitable complex medium components in the cultivation of S. peucetius var. caesius N47, which is an epsilon-rhodomycinone-accumulating mutant strain. epsilon-Rhodomycinone is a non-glycosylated precursor of doxorubicin. Best growth results were obtained with soy peptone and beef extract. A central composite face-centered (CCF) experimental design was constructed for the investigation of pH, temperature and dissolved oxygen (DO) effects on the cultivation growth phase. Another CCF was applied to the production phase to investigate the effects of aeration, pH, temperature and stirring rate on epsilon-rhodomycinone production. An increase in cultivation temperature increased both cell growth and glucose consumption rate. Best epsilon-rhodomycinone productivities were obtained in temperatures around 30 degrees C. DO control increased all growth phase responses, but aeration in the production phase coupled with pH decrease resulted in rapid epsilon-rhodomycinone decay in the medium. In non-aerated production phases a pH change resulted in better productivity than in experiments without pH change. A pH increase with a temperature decrease seemed most beneficial for productivity. This implies that dynamic control strategies in batch production of epsilon-rhodomycinone could increase the overall process productivity.

UI MeSH Term Description Entries
D010100 Oxygen An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration. Dioxygen,Oxygen-16,Oxygen 16
D012107 Research Design A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. Experimental Design,Data Adjustment,Data Reporting,Design, Experimental,Designs, Experimental,Error Sources,Experimental Designs,Matched Groups,Methodology, Research,Problem Formulation,Research Methodology,Research Proposal,Research Strategy,Research Technics,Research Techniques,Scoring Methods,Adjustment, Data,Adjustments, Data,Data Adjustments,Design, Research,Designs, Research,Error Source,Formulation, Problem,Formulations, Problem,Group, Matched,Groups, Matched,Matched Group,Method, Scoring,Methods, Scoring,Problem Formulations,Proposal, Research,Proposals, Research,Reporting, Data,Research Designs,Research Proposals,Research Strategies,Research Technic,Research Technique,Scoring Method,Source, Error,Sources, Error,Strategies, Research,Strategy, Research,Technic, Research,Technics, Research,Technique, Research,Techniques, Research
D003470 Culture Media Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN. Media, Culture
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D001709 Biotechnology Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. Biotechnologies
D013302 Streptomyces A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the ANTI-BACTERIAL AGENTS of practical value.
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D018943 Anthracyclines Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine. Anthracycline

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