title: Regulation of central carbon metabolism in Saccharomyces cerevisiae by metabolic inhibitors.
abstract: Metabolic inhibitors were applied for chemical regulation of central carbon metabolism in Saccharomyces cerevisiae. S. cerevisiae was treated with 10 metabolic inhibitors with various modes of action, and their activities were evaluated using a growth inhibition assay. Among the 6 active inhibitors, the effects of pyrazole (alcohol dehydrogenase inhibitor) and TTA (2-thenoyltrifluoloacetone, succinate dehydrogenase inhibitor) were analyzed in detail. The flask-scale batch-fermentation test showed that ethanol yield was reduced to 0.10 ± 0.01 g g⁻¹ and glycerol yield increased to 0.26 ± 0.01 g g⁻¹ on treatment with pyrazole at 5.0 g L⁻¹, indicating that multiple isozymes of alcohol dehydrogenase were simultaneously inhibited. The multi-targeted metabolic profiling analysis revealed that, although the TTA and pyrazole treatments affected the profiles of all central carbon metabolites in distinct manners, the level of fructose-1,6-bisphosphate commonly increased in the TTA- and pyrazole-treated S. cerevisiae by an unknown mechanism. These results demonstrate that chemical regulation of the central carbon metabolism could be used as an alternative tool to control microbial cell factories for bioproduction, or as a chemical probe to investigate the metabolic systems of useful microorganisms.
authors: Organization of Advanced Science and Technology, Kobe University, 1-1 Rokkodaicho, Nada, Kobe 657-8501, Japan. fmatsuda@ruby.kobe-u.ac.jp
authors: Fumio
authors: F
authors: Matsuda
authors: Tomokazu
authors: T
authors: Shirai
authors: Jun
authors: J
authors: Ishii
authors: Akihiko
authors: A
authors: Kondo
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives / Q000494:pharmacology; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D002244:Carbon / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism; D005285:Fermentation / Q000187:drug effects; D005990:Glycerol / Q000378:metabolism; D055442:Metabolome; D011720:Pyrazoles / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D013876:Thiophenes; D000096:Acetone; D000431:Ethanol; C031280:pyrazole; D002244:Carbon; D000426:Alcohol Dehydrogenase; D013385:Succinate Dehydrogenase; D005990:Glycerol