Transcriptional and metabolic responses of Bacillus subtilis to the availability of organic acids: transcription regulation is important but not sufficient to account for metabolic adaptation.

The soil bacterium Bacillus subtilis can use sugars or organic acids as sources of carbon and energy. These nutrients are metabolized by glycolysis, the pentose phosphate pathway, and the Krebs citric acid cycle. While the response of B. subtilis to the availability of sugars is well understood, much less is known about the changes in metabolism if organic acids feeding into the Krebs cycle are provided. If B. subtilis is supplied with succinate and glutamate in addition to glucose, the cells readjust their metabolism as determined by transcriptome and metabolic flux analyses. The portion of glucose-6-phosphate that feeds into the pentose phosphate pathway is significantly increased in the presence of organic acids. Similarly, important changes were detected at the level of pyruvate and acetyl coenzyme A (acetyl-CoA). In the presence of organic acids, oxaloacetate formation is strongly reduced, whereas the formation of lactate is significantly increased. The alsSD operon required for acetoin formation is strongly induced in the presence of organic acids; however, no acetoin formation was observed. The recently discovered phosphorylation of acetolactate decarboxylase may provide an additional level of control of metabolism. In the presence of organic acids, both types of analyses suggest that acetyl-CoA was catabolized to acetate rather than used for feeding the Krebs cycle. Our results suggest that future work has to concentrate on the posttranslational mechanisms of metabolic regulation.