Summary
The exact time course of phosphate consumption in a tetracycline production byStreptomyces aureofaciens has been determined. The data have been compared with model simulations according to a model proposed by Votruba et al. (1984). This led to a revision of his equation for the rate of phosphate consumption and to the proposal that phosphate is consumed proportionally to the growth rate. In contradiction to the model simulations it was found that the length of the time lag of the production is independent of the initial phosphate concentration. While the model explains the time lag through inhibition of the production by phosphate, the measured data show that there must be another or an additional reason for the lag. Simultaneously with the start of the production the organism changes from an organic substrate to ammonia as nitrogen source.
All experiments have been carried out in a bubble column of 651 working volume as fed batch fermentation. An autoanalyzer and a HPLC was coupled to the reactor for automatic measurement of phosphate, ammonia, sucrose and products in short intervals. Composition of the outlet gas, pH, pO2, temperature and weight of the substrate flasks were monitored on-line.
Similar content being viewed by others
References
Aharonowitz Y (1980) Nitrogen metabolite regulation of antibiotic biosynthesis. Ann Rev Microbiol 34:209–233
Aharonowitz Y (1983) Metabolic regulation of antibiotic biosynthesis effect of carbon, nitrogen and specific amino acid metabolism. In: Nisbet LJ, Winslanky DJ (eds) Bioactive microbial producs-2. Development and production, Academic Press, New York
Běhal V, Vanek Z, Hostalek Z, Ramadau A (1979) Synthesis and degradation of Proteins and DNA inStreptomyces aureofaciens. Folia Microbiol 24:211–216
Běhal V, Gregrova-Prusakova J, Hostalek Z (1982) Effect of inorganic phosphate and benzyl thiocyanate on the activity of anhydrotetracycline oxygenase inStreptomyces aureofaciens. Folia Microbiol 27:102–106
Colombo AL, Crespi-Perllino N, Grein A, Minghetti A, Spalla C (1981) Metabolic and genetic aspects of the relationship between growth and Tetracycline production inStreptomyces aureofaciens. Biotechnol Lett 3(2):71–76
Doskocil J, Hostalek Z, Kasparova J, Zajcek J, Herold M (1959) Development of Streptomyces aureofacies in submerged culture. J Biochem Microbiol Technol Engng 1:261–271
Duggar BM (1948) Aureomycin: a product of continuity search for new antibiotics. Ann NY Acad Sci 51:177–181
Hostalek Z (1984) The effect of interupted aeration, inmorganic phosphate and benzyl thiocyanate on CTC-biosynthesis. Folia Microbiol 9:78
Hostalek Z, Tobek I, Bobyk MA, Kulayew IS (1976) Role of ATP-Glucokinase and polyphosphate glucokinase inStreptomyces aureofaciens. Folia Microbiol 21:131–138
Hostalek Z (1980) Catabolite repression of antibiotic biosynthesis. Folia Microbiol 25:445
Janglova Z, Suchy J, Vanek Z (1969) Regulation of biosynthesis of secondary metabolites: VII. Intracellular ATP-concentrations inStreptomyces aureofaciens. Folia Microbiol 14:208–210
Jechova V, Curdova E, Hostalek Z (1982) Role of phosphatases in the biosynthesis of CTC inStreptomyces aureofaciens. Folia Microbiol 27:153–158
Malikova S, Szimuth J, Zelinka J (1972) Activity of DNA dependent RNA-Polymerase in metabolism ofStreptomyces aureofaciens. Biologia (Bratislava) 27:449–453
McCormick JRd, Sjolander NO, Johnson S, Doerschuk P (1959) J Bacteriol 77:475
Parada JL (1981) Growth inhibition ofStreptomyces species byl-serine and its effect on tetracycline biosynthesis. Appl Environ Microbiol 41:366–370
Prokofieva-Belgovskaya A, Popova L (1959) The influence of phosphorus on the development of Streptomyces aureofaciens and on its ability to produce Chlortetracycline. J Gen Microbiol 20:462–472
Ross A (1986) Probenahmesystem zur Ankopplung eines Autoanalyzers an einen Fermenter. In: Kula MR, Schügerl K, Wandrey Ch (eds) Technische Membranen in der Biotechnologie, GBF Monographien 9:221–224
Ross A, Schügerl K (1987) Application of elemental balances to complex fermentation systems. Proc 4th European Congress on Biotechnology 3:94
Simuth J, Hudec J, Chan HT, Dangi O, Zelinka J (1979) The synthesis of highly phosphorylated nucleotides, RNA and protein byStreptomyces aureofaciens. J Antibiotics 22:53
Virgilio A, Hengeller C (1980) Produzione di tetraciclina conStreptomyces psammoticus. II Farmaco 15(3):164
Votruba J, Běhal V (1984) A mathematical model of kinetics of the biosynthesis of tetracyclines. Appl Microbiol Biotechnol 19:153–156
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ross, A., Schügerl, K. Tetracycline production byStreptomyces aureofaciens: the time lag of production. Appl Microbiol Biotechnol 29, 174–180 (1988). https://doi.org/10.1007/BF01982898
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01982898