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Note: The writer of the following is an independent consultant and has no ties to, nor financial interest in, any industry or organization involved in the subject matter at hand.

Scope: Information and commentary on general chemistry, fermentation technology, antibiotics in general, tetracycline antibiotics in particular and life in general.

See also "Buffers in Fermentation" in my archive at: jandcmccormick

Buffers, Carbon dioxide and Oxygen in Fermentation.

Associated with the probable involvement of p[CO2] in optimal fermentation response is the requirement for a high level of oxygen supply to the living organisms.

In large scale fermentations, many stratagems have been utilized to attempt to increase the transport of oxygen from the gas phase to the submerged organisms that require it. Many combinations of agitators, baffles, fermentor geometries, oxygen enrichment of the gas phase, agitation power input, oxygen transfer agents, oxygen sources other than O2, and even inversion of the gas-liquid dispersion state have been investigated.

One of the simplest methods of oxygen transfer control has been perhaps the most neglected, namely, to increase (or decrease) the pressure under which the fermentor is operated. Most industrial scale fermentors are designed for sterilization with pressurized steam. And yet, the usual operating condition has been to vent the exhaust gas from the fermentor directly to the atmosphere so that the gas phase in the top of the fermentor itself is essentially at one atmosphere pressure. In addition, the air supply for fermentors is usually generated at well over one atmosphere, the pressure being lowered to attain the desired input flow rate by simple throttling at a control valve. Combining these several facts, it is a straight forward procedure to operate the fermentor at the sterilization pressure by the use of a back pressure control valve on the exhaust. In many cases, it is possible to double the partial pressure of oxygen in the gas phase (total pressure 14.7 psi above atmospheric pressure) and thereby double the gradient for the transfer of oxygen to the liquid phase, a goal difficult to achieve by the other stratagems mentioned above, and at virtually no increase in operating cost.

It is necessary, however, when pilot planting a superpressure fermentor experiment, to keep in mind the interactions of CO2, as discussed above. If the mass flow of air through the fermentor is kept at the same value as in the atmospheric fermentor, then not only will the oxygen partial pressure be doubled, but that of the biologically produced CO2 will at least be doubled also. The effect of this change in pCO2 will depend at any time on whether the fermentor is operating in a CO2 deficient, CO2 adequate, or CO2 excess domain (and the effect of these levels on pH and on crucial reaction rates). The CO2 domain at any time can be determined by examining the effect of a change in air mass flow and/or by enriching the gas stream with exogenous CO2. In summary, the effects of increased pO2 and of increased or decreased pCO2 can be studied by operating a fermentor at significantly higher gas pressure and at greater and less than reference (standard temperature and pressure) air mass flow rates.

Aeration of aerobic fermentations in stirred tank fermentors has been a much studied operation. It has been abundantly observed that the maximum oxygen demand in such systems coincides with later stages of the logarithmic growth phase, and, at least in two stage fermentations, where production of a desired metabolite reaches a peak rate well after the growth peak has been passed, oxygen demand diminishes during that productive phase. It is, in fact widely considered that oxygenation may well be the limiting factor in generating increased levels of cell mass. In other words, as ever richer media are developed in a given system, eventually a point is reached where the growth rate is limited by the oxygen supply and further enrichment of the medium is to no avail. One method of control of growth rate appears not to have been extensively exploited. This consists of temperature programing, based on dissolved oxygen level, lowering the set temperature as required to maintain a greater-than-zero dissolved oxygen level. (Temperature programming is fairly common in antibiotic fermentations, but the usual program is to employ a higher initial temperature, in the growth phase, to achieve a maximum growth rate, and then a lower temperature in the production phase, "because it works".)

J. R. D. Mcormick Biographical Data and Experience:

Born St. Albans, WVa; Married, wife Catherine; son, Joshua.

Education: B. Sc.(Chemistry), Rensselaer Polytechnic Institute, Ph. D. (Organic Chemistry), UCLA

Professional History: Pharmaceutical Chemist, Winthrop Chemical Company, Rensselaer, NY.

Pharmaceutical Chemist, Lederle Laboratories of American Cyanamid, Inc. Pearl River , NY

Internal Consultant (Research Fellow) Lederle Laboratories.

Independent Consultant: General Chemistry and Biochemistry, Fermentation Technology, Antibiotics, Tetracycline Antibiotics.

Publications: Over forty articles and presentations on various aspects of tetracyclines chemistry and biochemistry. Forty U.S. Patents on chemical processes and products in the fields of vitamins, antibiotics, and unique chemical substances.

Special current interests: Fermentation technology, Cellulose chemistry, alternative energy systems, biomass production and uses.

Comments?, Questions? Arguments? E-mail me at the address above.

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Last updated August 7, 2002 by J. R. D. McCormick