The biosynthesis of tetracycline

Abstract

It was initially assumed that the tetracycline nucleus originated by the polyketide pathway from acetyl-or malonyl-CoA. Evaluation of the results of experiments with labelled precursors and on the regulation of presumed key enzyme systems, however, has led to the conclusion that the situation is more complex than was first thought. It is suggested that chlortetracycline does not fit into the category of the so-called secondary metabolites and should be regarded rather as an 'excessive metabolite' produced by variation in the control of certain key primary pathways. The experimental evidence on control of pathways during the various phases of the bacterial growth cycle is reviewed.

Comparative aspects of development and differentiation in actinomycetes.

“…With tetracyclines (529), maximal accumulation of antibiotic was found to occur during "production phase." At that time, as shown by these authors, the nutritional environment was changed drastically, because the phosphorus source was completely exhausted.…”

Biosynthesis of Oxytetracycline by Streptomyces rimosus: Past, Present and Future Directions in the Development of Tetracycline Antibiotics

“…Very productive work on the genetics of TC-producing strains, as well as on the biosynthesis of CTC and OTC was carried out by academic groups in the former Czechoslovakia and by Croatian researchers at the Faculty of Food Technology and Biotechnology at the University of Zagreb (43). Russian scientists from the All--Union Research Institute for Antibiotics in Moscow also contributed to the area of genetics of OTC production by S. rimosus; their work was mostly published in Russian journals (44).…”

“…Environmental factors, such as carbon, nitrogen, inorganic phosphate, metal ion and other nutrient sources, cultivation condition parameters, such as pH and aeration (dO 2 ), and cultivation methods in general, may aff ect the timing and the extent of TC production (43,75,76). Media containing high concentrations of starch as a carbon source are generally used in fermentation processes for the production of OTC with S. rimosus at the industrial level, although vegetable oil can also be used as a carbon source.…”

“…Media containing high concentrations of starch as a carbon source are generally used in fermentation processes for the production of OTC with S. rimosus at the industrial level, although vegetable oil can also be used as a carbon source. It was shown that S. rimosus produces OTC abundantly when subjected to phosphate starvation (43,75,76). McDowall et al (77) reported that the sequences of the promoter regions in the S. rimosus 4018 strain (now designated as DNA sequence encoding oxyI, oxyJ, oxyR, oxyS and oxyA genes (40)) contain tandem repeats that are similar to the DNA-binding sites of Streptomyces antibiotic regulatory protein (SARP) transcription activators.…”