TY  - JOUR
A1  - Liang, Chunguang
A1  - Rios-Miguel, Ana B.
A1  - Jarick, Marcel
A1  - Neurgaonkar, Priya
A1  - Girard, Myriam
A1  - François, Patrice
A1  - Schrenzel, Jacques
A1  - Ibrahim, Eslam S.
A1  - Ohlsen, Knut
A1  - Dandekar, Thomas
T1  - Staphylococcus aureus transcriptome data and metabolic modelling investigate the interplay of Ser/Thr kinase PknB, its phosphatase Stp, the glmR/yvcK regulon and the cdaA operon for metabolic adaptation
JF  - Microorganisms
N2  - Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB\(^+\)) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB\(^−\)) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.
KW  - metabolism
KW  - flux balance analysis
KW  - phosphorylation
KW  - regulation
KW  - riboswitch
KW  - PknB
KW  - Stp
KW  - yvcK/glmR operon
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248459
SN  - 2076-2607
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Schwender, Joerg
A1  - Koenig, Christina
A1  - Klapperstueck, Matthias
A1  - Heinzel, Nicolas
A1  - Munz, Eberhard
A1  - Hebbelmann, Inga
A1  - Hay, Jordan O.
A1  - Denolf, Peter
A1  - De Bodt, Stefanie
A1  - Redestig, Henning
A1  - Caestecker, Evelyne
A1  - Jakob, Peter M.
A1  - Borisjuk, Ljudmilla
A1  - Rolletschek, Hardy
T1  - Transcript abundance on its own cannot be used to infer fluxes in central metabolism
JF  - Frontiers in Plant Science
N2  - An attempt has been made to define the extent to which metabolic flux in central plant metabolism is reflected by changes in the transcriptome and metabolome, based on an analysis of in vitro cultured immature embryos of two oilseed rape (Brassica napus) accessions which contrast for seed lipid accumulation. Metabolic flux analysis (MFA) was used to constrain a flux balance metabolic model which included 671 biochemical and transport reactions within the central metabolism. This highly confident flux information was eventually used for comparative analysis of flux vs. transcript (metabolite). Metabolite profiling succeeded in identifying 79 intermediates within the central metabolism, some of which differed quantitatively between the two accessions and displayed a significant shift corresponding to flux. An RNA-Seq based transcriptome analysis revealed a large number of genes which were differentially transcribed in the two accessions, including some enzymes/proteins active in major metabolic pathways. With a few exceptions, differential activity in the major pathways (glycolysis, TCA cycle, amino acid, and fatty acid synthesis) was not reflected in contrasting abundances of the relevant transcripts. The conclusion was that transcript abundance on its own cannot be used to infer metabolic activity/fluxes in central plant metabolism. This limitation needs to be borne in mind in evaluating transcriptome data and designing metabolic engineering experiments.
KW  - oilseeds
KW  - lipid biosynthesis
KW  - heterotrophic arabidopsis cells
KW  - central carbon metabolism
KW  - gene-expression data
KW  - targeted metabolite profiling
KW  - central metabolism
KW  - flux balance analysis
KW  - C-13-metabolic flux analysis
KW  - Brassica napus
KW  - RNA-SEQ
KW  - developing oilseeds
KW  - saccharomyces cerevisiae
KW  - maize kernels
KW  - embryo
KW  - seed
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114586
SN  - 1664-462X
N1  - Funding information:
Bayer Crop Science NV; Deutsche Forschungsgemeinschaft [BO-1917/4-1]; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division [DEACO298CH10886]
VL  - 5
ER  -