History of Continuous Fermentation

Many systems in nature have input and output flows and operate over long time periods; in this sense they are continuous bioprocesses if active microorganisms are present. Bioprocesses for useful products probably were rarely continuous because contamination is likely when there are no precautions against entry of foreign organisms. Until the discoveries of Louis Pasteur, it was not appreciated that microorganisms were the causes of disease and spoilage. Ways of keeping feed streams to a bioprocess uncontaminated were not developed. Until the times of Semmelweiss, surgeons did not even wash their hands before moving to the next patient. Supperation and puss while recovering from an incision were considered normal.

In very early times, waste treatment was continuous. However, the main processes were dumping wastes on land or into natural waters. Biological waste treatment in channels or vessels is roughly 100 years old and is predominantly continuous because the wastes keep coming.

The concept of continuous culture dates from the 19th Century when a continuous process for the conversion of waste beers and wines to vinegar was developed. In this reactor, natural acetic acid bacterial populations were immobilized on wood shavings. Beer or wine was added through the top of the reactor and allowed to trickle through the shavings. Vinegar was collected at an outlet located at the base of the reactor. The acetic acid discourages contamination at conditions where the acetobacter thrive.

The chemostat invented in the early 1940's marked the advent of serious continuous fermentation. The use of continuous stirred tank reactor to extend duration of culture of microbes was developed in the 1950s by Novick and Szilard and Monod. The realization that a CSTR could be used to maintain microbial growth at a steady state value, that could be varied from any growth rate up to the maximum µmax, was an important advance; it broke the traditional thinking at the time that stable microbial growth was only possible at the maximum rate, corresponding to the minimum doubling time found in batch cultures. Subsequently, the use of a well-mixed continuous reactor to study microbial physiology led to important advances in understanding the cell cycle, metabolic regulation and microbial product formation.

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