Carbon Catabolite Repression in Yeast is Not Limited to Glucose

Simpson-Lavy, Kobi J.; Kupiec, Martin

doi:10.1038/s41598-019-43032-w

Cited by 39 publications

(19 citation statements)

References 69 publications

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“…In addition, ethanol catabolism ( ADH2 , ALD5 ) were also inhibited in the presence of acetate as the sole carbon source. Alcohol dehydrogenase ( ADH2 ) catalyses the breakdown of ethanol into acetaldehyde, which could be converted to acetate by aldehyde dehydrogenase ( ALD5 ) [ 46 , 70 ]. It is worth to highlight that minor discrepancies between transcript and protein abundances were observed in pathways associated with biosynthesis of secondary metabolites and amino acids.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata

et al. 2021

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Background Emergence of Candida glabrata, which causes potential life-threatening invasive candidiasis, has been widely associated with high morbidity and mortality. In order to cause disease in vivo, a robust and highly efficient metabolic adaptation is crucial for the survival of this fungal pathogen in human host. In fact, reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection. Methods In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches. Results Collectively, a total of 1482 transcripts (26.96%) and 242 proteins (24.69%) were significantly up- or down-regulated. Both transcriptome and proteome data revealed that the regulation of alternative carbon metabolism in C. glabrata resembled other fungal pathogens such as Candida albicans and Cryptococcus neoformans, with up-regulation of many proteins and transcripts from the glyoxylate cycle and gluconeogenesis, namely isocitrate lyase (ICL1), malate synthase (MLS1), phosphoenolpyruvate carboxykinase (PCK1) and fructose 1,6-biphosphatase (FBP1). In the absence of glucose, C. glabrata shifted its metabolism from glucose catabolism to anabolism of glucose intermediates from the available carbon source. This observation essentially suggests that the glyoxylate cycle and gluconeogenesis are potentially critical for the survival of phagocytosed C. glabrata within the glucose-deficient macrophages. Conclusion Here, we presented the first global metabolic responses of C. glabrata to alternative carbon source using transcriptomic and proteomic approaches. These findings implicated that reprogramming of the alternative carbon metabolism during glucose deprivation could enhance the survival and persistence of C. glabrata within the host.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata

et al. 2021

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“…Our discovery that acetate specifically induces the prion state in wine strain UCD932 is also an intriguing observation ( Ramakrishnan et al, 2016 ).). Acetate functions as a stress signal within the cell, not at the cell surface ( Simpson-Lavy and Kupiec, 2019a , b ). Acetate resistant membranes are higher in PI content ( Guo et al, 2018 ), consistent with what is observed for [ GAR + ] cells.…”

Section: Discussionmentioning

confidence: 99%

Downshifting Yeast Dominance: Cell Physiology and Phospholipid Composition Are Altered With Establishment of the [GAR+] Prion in Saccharomyces cerevisiae

et al. 2020

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Establishment of the [GAR + ] prion in Saccharomyces cerevisiae reduces both transcriptional expression of the HXT3 hexose transporter gene and fermentation capacity in high sugar conditions. We evaluated the impact of deletion of the HXT3 gene on the expression of [GAR + ] prion phenotype in a vineyard isolate, UCD932, and found that changes in fermentation capacity were observable even with complete loss of the Hxt3 transporter, suggesting other cellular functions affecting fermentation rate may be impacted in [GAR + ] strains. In a comparison of isogenic [GAR + ] and [gar − ] strains, localization of the Pma1 plasma membrane ATPase showed differences in distribution within the membrane. In addition, plasma membrane lipid composition varied between the two cell types. Oxygen uptake was decreased in prion induced cells suggesting membrane changes affect plasma membrane functionality beyond glucose transport. Thus, multiple cell surface properties are altered upon induction of the [GAR + ] prion in addition to changes in expression of the HXT3 gene. We propose a model wherein [GAR + ] prion establishment within a yeast population is associated with modulation of plasma membrane functionality, fermentation capacity, niche dominance, and cell physiology to facilitate growth and mitigate cytotoxicity under certain environmental conditions. Down-regulation of expression of the HXT3 hexose transporter gene is only one component of a suite of physiological differences. Our data show the [GAR + ] prion state is accompanied by multiple changes in the yeast cell surface that prioritize population survivability over maximizing metabolic capacity and enable progeny to establish an alternative adaptive state while maintaining reversibility.

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“…The presence of carbon sources with efficient assimilation like glucose promotes rapid microbial growth. However, it simultaneously prevents other carbon source’s catabolism by a mechanism called carbon catabolite repression (CCR) ( Simpson-Lavy and Kupiec, 2019 ). This mechanism is one of the most conserved ones reported in various bacteria, including actinobacteria.…”

Section: Protein Modification By Acetylation Of Lysine Residues: the mentioning

confidence: 99%

Modulation of Gene Expression in Actinobacteria by Translational Modification of Transcriptional Factors and Secondary Metabolite Biosynthetic Enzymes

2021

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Different types of post-translational modifications are present in bacteria that play essential roles in bacterial metabolism modulation. Nevertheless, limited information is available on these types of modifications in actinobacteria, particularly on their effects on secondary metabolite biosynthesis. Recently, phosphorylation, acetylation, or phosphopantetheneylation of transcriptional factors and key enzymes involved in secondary metabolite biosynthesis have been reported. There are two types of phosphorylations involved in the control of transcriptional factors: (1) phosphorylation of sensor kinases and transfer of the phosphate group to the receiver domain of response regulators, which alters the expression of regulator target genes. (2) Phosphorylation systems involving promiscuous serine/threonine/tyrosine kinases that modify proteins at several amino acid residues, e.g., the phosphorylation of the global nitrogen regulator GlnR. Another post-translational modification is the acetylation at the epsilon amino group of lysine residues. The protein acetylation/deacetylation controls the activity of many short and long-chain acyl-CoA synthetases, transcriptional factors, key proteins of bacterial metabolism, and enzymes for the biosynthesis of non-ribosomal peptides, desferrioxamine, streptomycin, or phosphinic acid-derived antibiotics. Acetyltransferases catalyze acetylation reactions showing different specificity for the acyl-CoA donor. Although it functions as acetyltransferase, there are examples of malonylation, crotonylation, succinylation, or in a few cases acylation activities using bulky acyl-CoA derivatives. Substrates activation by nucleoside triphosphates is one of the central reactions inhibited by lysine acetyltransferases. Phosphorylation/dephosphorylation or acylation/deacylation reactions on global regulators like PhoP, GlnR, AfsR, and the carbon catabolite regulator glucokinase strongly affects the expression of genes controlled by these regulators. Finally, a different type of post-translational protein modification is the phosphopantetheinylation, catalized by phosphopantetheinyl transferases (PPTases). This reaction is essential to modify those enzymes requiring phosphopantetheine groups like non-ribosomal peptide synthetases, polyketide synthases, and fatty acid synthases. Up to five PPTases are present in S. tsukubaensis and S. avermitilis. Different PPTases modify substrate proteins in the PCP or ACP domains of tacrolimus biosynthetic enzymes. Directed mutations of genes encoding enzymes involved in the post-translational modification is a promising tool to enhance the production of bioactive metabolites.

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Carbon Catabolite Repression in Yeast is Not Limited to Glucose

Cited by 39 publications

References 69 publications

Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata

Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata

Downshifting Yeast Dominance: Cell Physiology and Phospholipid Composition Are Altered With Establishment of the [GAR+] Prion in Saccharomyces cerevisiae

Modulation of Gene Expression in Actinobacteria by Translational Modification of Transcriptional Factors and Secondary Metabolite Biosynthetic Enzymes

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