Abstract
This study explores the relation between biomass-specific succinic acid
(SA) production rate and specific growth rate of an engineered
industrial strain of Saccharomyces cerevisiae, with the aim to
investigate the extent to which growth and product formation can be
uncoupled. Ammonium-limited aerobic chemostat and retentostat cultures
were grown at different specific growth rates under industrially
relevant conditions, i.e., at a culture pH of 3 and with sparging of a
1:1 CO2-air mixture. Biomass-specific SA production rates decreased
asymptotically with decreasing growth rate. At near-zero growth rates,
the engineered strain maintained a stable biomass-specific SA production
rate for over 500 h, with a SA yield on glucose of 0.61
mol.mol-1. These results demonstrate that uncoupling
of growth and SA production could indeed be achieved. A linear relation
between biomass-specific SA production rate and glucose consumption rate
indicated a coupling of SA production rate and the flux through primary
metabolism. The low culture pH resulted in an increased death rate,
which was lowest at near-zero growth rates. Nevertheless, a significant
amount of non-viable biomass accumulated in the retentostat cultures,
thus underlining the importance of improving low-pH tolerance in further
strain development for industrial SA production with S.
cerevisiae.