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Self-cycling fermentation (SCF), a cyclic process in which cells, on average, divide once per cycle, has been shown to lead to whole-culture synchronization and improvements in productivity during bioconversion. Previous studies have shown that the completion of synchronized cell replication sometimes occurs simultaneously with depletion of the limiting nutrient. However, cases in which the end of cell doubling occurred before limiting nutrient exhaustion were also observed. In order to better understand the impact of these patterns on bioprocessing, we investigated the growth of Saccharomyces cerevisiae and Escherichia coli in long- and short-cycle SCF strategies. Three characteristic events were identified during SCF cycles: (1) an optimum in control parameters, (2) the time of completion of synchronized cell division, and (3) the depletion or plateau of the limiting nutrient. Results from this study and literature led to the identification of three potential trends in SCF cycles: (A) co-occurrence of the three key events, (B) cell replication ending prior to the co-occurrence of the other two events, and (C) depletion or plateau of the limiting nutrient occurring later than the co-occurrence of the other two events. Based on these observations, microbial physiological differences were analyzed and a novel definition for SCF is proposed.

Self-cycling fermentation (SCF), a cyclic process in which cells divide once per cycle, has been shown to lead to improvements in productivity during bioconversion and, often, whole-culture synchronization. Previous studies have found that in some cases, the completion of synchronized cell replication occurred simultaneously with depletion of a limiting nutrient. However, exceptions were also observed when the end of cell doubling occurred before the exhaustion of the limiting nutrient. In order to better understand the underlying mechanisms and impacts of these growth patterns on bioprocessing, we investigated the growth of Escherichia coli and Saccharomyces cerevisiae in long- and short-cycle SCF strategies. Three characteristic events linked to SCF cycles were identified: (1) the completion of synchronized cell replication, (2) the depletion or a plateau of the limiting nutrient, and (3) characteristic points of control parameters (e.g., the minimum of dissolved oxygen and the maximum of carbon dioxide evolution rate). Three major trends stemming from this study and SCF literature were observed: (A) co-occurrence of the three key events in SCF cycles, (B) cycles for which cell replication ended prior to the co-occurrence of the other two events, and (C) cycles for which the time of depletion or a plateau of the limiting nutrient occurred later than the concurrence of the other two events. Based on these observations, a novel definition for SCF is proposed.