Control of specific growth rate in Saccharomyces cerevisiae

1 Triple J Group for Molecular Cell Physiology, Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa 2 Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK 3 University of Amsterdam, Swammerdam Institute for Life Sciences, Department of Molecular and Microbial Physiology, Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands In this contribution we resolve the long-standing dispute whether or not the Monod constant (K S ), describing the overall affinity of an organism for its growth-limiting substrate, can be related to the affinity of the transporter for that substrate (K M ). We show how this can be done via the control of the transporter on the specific growth rate; they are identical if the transport step has full control. The analysis leads to the counter-intuitive result that the affinity of an organism for its substrate is expected to be higher than the affinity of the enzyme that facilitates its transport. Experimentally, we show this indeed to be the case for the yeast Saccharomyces cerevisiae , for which we determined a K M value for glucose more than two times higher than the K S value in glucose-limited chemostat cultures. Moreover, we calculated that at glucose concentrations of 0.03 and 0.29 mM, the transport step controls the specific growth rate at 78 and 49 %, respectively. Correspondence J. L. Snoep jls{at}sun.ac.za