Production of cyclic adenosine monophosphate by Arthrobacter sp. A302 using fed-batch fermentation with pH-shift control

Abstract

The production of cyclic adenosine monophosphate (cAMP) by Arthrobacter sp. A302 was studied in a 5L stirred tank fermentor under a range of pH values (6.5-8.0) and glucose feeding rates. In batch fermentation under a controlled pH, the optimum pH for cell growth was 7.5 with dry cell density (X) of 11.43gL, and the optimum pH for cAMP accumulation was 7.0 with cAMP concentration of 7.41gL. In order to achieve the high X and cAMP yield simultaneously, a pH-shift control strategy was proposed based on kinetic analysis of specific cell growth rate (μ) and specific cAMP formation rate (q ( s )). In this method, pH was controlled to 7.0 for the first 30h of fermentation, and then subsequently shifted to 7.5 and maintained until the end of the process. Application of this approach significantly enhanced the cAMP concentration. Thereafter, cAMP production was further improved by combining the above-mentioned pH-control system and fed-batch process with glucose at a constant feeding rate of 1.0gL(-1)h(-1). Under optimum conditions, the final cAMP production was 10.87gL, which is 110.0, 46.7, and 27.7% higher than that of the pH-uncontrolled, pH-controlled, and pH-shift controlled methods, respectively.