imary metabolism. A slow down of growth and of the whole primary metabolism would logically be accompanied by a decrease of the ATP level.in the case of ATP, the role of cAMP in the metabolism of antibiotic producers was also studied, especially in connection with the glucose regulation. Hitherto, no indication has been obtained suggesting a significant role of cAMP in the regulation of antibiotic production.
antibiotic medicine microorganisms
1.2.3 Reception of signals from environment
The way of reception of signals from the environment, so that they would be available to the genetic material of the cell to result in the initiation of the antibiotic synthesis, is known quite well. It does not significantly differ from the trasduction of signals for other metabolic processes. Catabolite repression signals or those signalling the depletion of nitrogen or phosphate or the initiation of sporulation are transducted via two-component, signal proteins [22]. In spite of some structural varieties, these proteins are characterized by general mechanistic features and conserved amino acid sequences. The two-component system consists of a cytoplasmic membrane-linked, sensor-transmitter protein and a response-regulator protein, located in the cytoplasm. The sensor-transmitter is composed of a sensor domain located near its N-end; the N-end is found outside the cytoplasm. A specific effector is capable of binding directly to this N-end. The transmitter domain is located in the cytoplasm to be linked to the sensor domain via a hydrophobic, amino acid sequence stretching across the membrane. The sensor-transmitter proteins are normal histidine-protein kinases, capable of autophosphorylation at its C-end on receiving a proper signal.
Transcription initiation of structural genes. Regulatory proteins, having been bound to specific DNA sequences and having interacted with RNA polymerase, start the transcription. Regulatory proteins that activate the transcription of structural genes are probably synthesized already during the lag phase. Their binding to DNA and a subsequent biosynthesis of the antibiotic depend mainly on the composition of the growth medium. Provided inorganic phosphate is present in the medium, the activator becomes phosphorylated and thus incapable of binding to DNA. In contrast, for example, the activator of the synthesis of glutamine synthetase, a key enzyme of the assimilation of ammonium salts from the medium and, consequently, of utmost importance for proteosynthesis, is able to bind to DNA only in a phosphorylated form.
One can hypothesize that a depletion of inorganic phosphate from the medium does not stop proteosynthesis as a result of a lack of phosphate in the cell for the biosynthesis of cellular structures, as the phosphate limitation is normally explained, but rather the presence or absence of phosphate in the medium causes respective activation or repression of the activators of the enzyme syntheses in primary or secondary metabolisms.
This idea is also supported by the fact that enzymes of secondary metabolism were synthesized and the antibiotics produced immediately after the phosphate, that had been added at the beginning of the production phase, was depleted from the medium and deposited in the cell [23].
. 3 Technology of antibiotic production
Some antibiotics are commercially produced on a ton scale. The fermentation process during which microorganisms produce antibiotics is carried out in fermentors having a volume of several tens of cubic meters. As in any fermentation process, a conserved strain is used, that is first propagated in the laboratory and then in a plant fermentor. The cells are then used to inoculate production fermentors. The inoculum is most often put into a 10 to 20-fold volume of the fresh medium.
Isolation of a producing microorganism from one cell. The spores are transferred from an agar slope into a volume of 10 ml of sterile H 2 O and, after homogenization, the suspension is diluted to contain 30-50 spores in 1 ml. A volume of 0.25 ml of this suspension is transferred on the surface of a suitable agar medium on a Petri dish and spread with a sterile glass stick. Colonies, each of which originates from one cell, grow on the agar. The individual colonies are re-inoculated to agar slopes and their antibiotic production is tested.
. 3.1 Conservation of microorganisms
If cultures are conserved for a long time on agar slopes, being repeatedly transferred from one slope to another, they can degenerate and lose valuable technological properties. Two types of conservation are recommended for long term storage of strains: l...
