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The growth of yeast cells to high densities at low, but constant, oxygen concentrations is difficult because the cells themselves respire oxygen; hence, as cell mass increases, so does oxygen consumption. To circumvent this problem, we have designed a system consisting of a computer-controlled gas flow train that adjusts oxygen concentration in the gas flow to match cellular demand. It does this by using a proportional-integral-differential algorithm in conjunction with a three-way valve to mix two gases, adjusting their proportions to maintain the desired oxygen concentration. By modeling yeast cell yields at intermediate to low oxygen concentrations, we have found that cellular respiration declines with oxygen concentration, most likely because of a decrease in the expression of genes for respiratory proteins. These lowered rates of oxygen consumption, together with the gas flow system described here, allow the growth of yeast cells to high densities at low oxygen concentrations. This system can also be used to grow cells at any desired oxygen concentration and for regulated shifts between oxygen concentrations.

A Fermentor System for Regulating Oxygen at Low Concentrations in Cultures of Saccharomyces cerevisiae