Estimation of P-to-O ratio in Bacillus subtilis and its influence on maximum riboflavin yield.
Simultaneous growth and riboflavin overproduction were investigated using a previously developed stoichiometric model of Bacillus subtilis metabolism. A fit of model predictions to experimental data was used to obtain estimates of fundamental energetic parameters of B. subtilis. Although multiple solutions describe the experimental data, evidence for a P-to-O ratio of about 1(1/3) mole of ATP produced per atom of oxygen consumed in oxidative phosphorylation was provided by genomic analysis of electron transport components, because no homologue of the proton-translocating NADH dehydrogenase I was found in the B. subtilis genome database. These results allow us to devise a rational metabolic engineering strategy to improve riboflavin production. The potential influence of increased energy coupling in oxidative phosphorylation on riboflavin yield is discussed. Higher coupling is most significant under carbon-limiting conditions in slow-growing cells, that is, in fed-batch processes of industrial interest.
Institute of Biotechnology, ETH Zürich, CH-8093 Zürich, Switzerland.
U
U
Sauer
J E
JE
Bailey
D000255:Adenosine Triphosphate / Q000378:metabolism; D001412:Bacillus subtilis / Q000378:metabolism*; D002455:Cell Division; D004583:Electrons; D004734:Energy Metabolism; D010100:Oxygen / Q000378:metabolism*; D010758:Phosphorus / Q000378:metabolism*; D010766:Phosphorylation; D012256:Riboflavin / Q000096:biosynthesis*
D010758:Phosphorus; D000255:Adenosine Triphosphate; D010100:Oxygen; D012256:Riboflavin