Abstract
Theoretical and experimental studies have indicated that cyclic propagation strategies, such as repeated batch cultivation, can produce significant increases in product yield. However, theoretical studies suggest that cyclic strategies are highly cell cycle dependent. Therefore, the objective of this research is to find experimental evidence of that dependency and how it affects the performance of the culture. In repeated batch mode, the culture is grown as a batch for a period of time (the dilution cycle time, DCT) after which a fraction of the culture is withdrawn and replaced from the reactor (the harvest fraction, HF) with fresh medium. The process is then repeated. In this study, six repeated batch experiments (127 cycles) using Schizosac-charomyces pombe were performed with a constant HF=0.8 and DCT=12 hrs. By obtaining the cell and glucose concentration of samples taken from the reactor at the beginning and end of each cycle, it was found that, even under carefully controlled conditions two potential responses can be exhibited by the system: constant or variable with respect to the final cell concentration of each cycle. It was also found that experiments with constant response obtained a larger yield (Yx/s = 5.45x10e5 cells/mg) compared to that of variable response experiments (Yx/s = 4.45x10e5 cells/mg). In addition, when frequent sampling was performed during the course of some cycles, the constant response experiments exhibited exponential growth, whereas variable response experiments exhibited partial synchronisation as well as exponential growth. In the exponential growth cycles, a R2 = 0.98 was obtained from a regression during the period of constant growth, whereas a R2 =0.92 was obtained for cycles exhibiting partial synchronisation. From the data obtained, it was concluded that cell cycle related phenomenon affected the performance of repeated batch cultivation in terms of its yield (cell concentration to glucose consumed); and that the variable response observed in some experiments was driven by partial synchronisation of the culture.