Jv. Straight et D. Ramkrishna, MODELING OF BACTERIAL-GROWTH UNDER MULTIPLY-LIMITING CONDITIONS - EXPERIMENTS UNDER CARBON-LIMITING OR AND NITROGEN-LIMITING CONDITIONS/, Biotechnology progress, 10(6), 1994, pp. 588-605
As the Limiting substrate is altered, a microorganism's internal struc
ture is also altered by invoking different metabolic pathways for the
utilization of the limiting substrate. Transitions between pathways ar
e moderated by the processes of metabolic regulation and are observed
under steady-state and transient conditions. Under nitrogen-limited st
eady-state conditions, the effects of overflow metabolism are observed
in the form of polysaccharide synthesis and excess carbon oxidation,
two phenomena that are not observed under carbon-limited conditions. F
urthermore, during transient periods following dilution rate shifts, m
etabolic lags are observed to be a function of the size of the shift a
s well as the limiting substrate. The latter observation indicates the
preference of one reaction pathway over another as the status of gluc
ose or NH4+ is altered from limiting to nonlimiting. This paper presen
ts steady-state and transient results from continuous culture experime
nts using Escherichia coli W. Singly-Limiting conditions, when either
glucose or ammonia is the limiting substrate, are investigated. Transi
ent conditions are created by quickly increasing or decreasing the dil
ution rate of the fermenter. By utilizing the control strategies ident
ified by Straight and Ramkrishna (1994) for regulating the processes c
ommonly found within metabolic pathways, a cybernetic model is develop
ed and compared to the steady-state and transient experimental results
. Due to the incorporation of metabolic pathways, the development of t
he model accounts for lumped biosynthetic intermediates in addition to
key enzymes that catalyze different cellular processes. The model als
o accounts for an internal resource that is optimally allocated toward
the synthesis of the key enzymes. Furthermore, the model incorporates
the effects of maintenance processes and overflow metabolism. Upon in
corporating nitrogen utilization, the kinetic aspects of the model do
not explicitly reduce to those of previous cybernetic models; however,
the regulatory structure is in complete agreement with previous cyber
netic models proposed for carbon utilization.