title: Difference in C3-C4 metabolism underlies tradeoff between growth rate and biomass yield in Methylobacterium extorquens AM1.
abstract: Two variants of Methylobacterium extorquens AM1 demonstrated a trade-off between growth rate and biomass yield. In addition, growth rate and biomass yield were also affected by supplementation of growth medium with different amounts of cobalt. The metabolism changes relating to these growth phenomena as well as the trade-off were investigated in this study. (13)C metabolic flux analysis was used to generate a detailed central carbon metabolic flux map with both absolute and normalized flux values.
  
  
  
  The major differences between the two variants occurred at the formate node as well as within C3-C4 inter-conversion pathways. Higher relative fluxes through formyltetrahydrofolate ligase, phosphoenolpyruvate carboxylase, and malic enzyme led to higher biomass yield, while higher relative fluxes through pyruvate kinase and pyruvate dehydrogenase led to higher growth rate. These results were then tested by phenotypic studies on three mutants (null pyk, null pck mutant and null dme mutant) in both variants, which agreed with the model prediction.
  
  
  
  In this study, (13)C metabolic flux analysis for two strain variants of M. extorquens AM1 successfully identified metabolic pathways contributing to the trade-off between cell growth and biomass yield. Phenotypic analysis of mutants deficient in corresponding genes supported the conclusion that C3-C4 inter-conversion strategies were the major response to the trade-off.
authors.affiliation: Department of Chemical Engineering, University of Washington, 616 NE Northlake Place, Benjamin Hall Room 440, Seattle, 98105, WA, USA.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Chemical Engineering, University of Washington, 616 NE Northlake Place, Benjamin Hall Room 440, Seattle, 98105, WA, USA.|eScience Institute, University of Washington, 616 NE, Northlake Place, Seattle, 98195, WA, USA.
authors.forename: David A C
authors.initials: DA
authors.lastname: Beck
authors.affiliation: Department of Chemical Engineering, University of Washington, 616 NE Northlake Place, Benjamin Hall Room 440, Seattle, 98105, WA, USA. lidstrom@uw.edu.|Department of Microbiology, University of Washington, 616 NE, Northlake Place, Seattle, 98195, WA, USA. lidstrom@uw.edu.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Lidstrom
mesh_terms: D018533:Biomass; D002245:Carbon Dioxide / Q000378:metabolism; D003035:Cobalt / Q000378:metabolism; D005561:Formates / Q000378:metabolism; D005798:Genes, Bacterial; D008025:Ligases / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D064688:Metabolic Flux Analysis; D000432:Methanol / Q000378:metabolism; D020601:Methylobacterium extorquens / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D009154:Mutation; D010084:Oxidation-Reduction; D010641:Phenotype; D010730:Phosphoenolpyruvate Carboxylase / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism
chemical_list: D005561:Formates; D008293:Malates; D011768:Pyruvate Dehydrogenase Complex; C030544:formic acid; D002245:Carbon Dioxide; D003035:Cobalt; C030298:malic acid; D011770:Pyruvate Kinase; D010730:Phosphoenolpyruvate Carboxylase; D008025:Ligases; D000432:Methanol
keywords: Cobalt; Metabolic flux analysis; Methylobacterium extorquens AM1; Methylotrophy; Physiological trade-off