scholarly journals Transcriptomic Analysis of the Influence of Methanol Assimilation on the Gene Expression in the Recombinant Pichia pastoris Producing Hirudin Variant 3

Genes ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 606 ◽  
Author(s):  
Li ◽  
Ma ◽  
Xu ◽  
Wang ◽  
Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Pichia Pastoris ◽  
Carbon Metabolism ◽  
Fermentation Broth ◽  
Alcohol Oxidase ◽  
Central Carbon Metabolism ◽  
Recombinant Pichia Pastoris ◽  
Central Carbon ◽  
Almost All

Hirudin and its variants, as strong inhibitors against thrombin, are present in the saliva of leeches and are recognized as potent anticoagulants. However, their yield is far from the clinical requirement up to now. In this study, the production of hirudin variant 3 (HV3) was successfully realized by cultivating the recombinant Pichia pastoris GS115/pPIC9K-hv3 under the regulation of the promoter of AOX1 encoding alcohol oxidase (AOX). The antithrombin activity in the fermentation broth reached the maximum value of 5000 ATU/mL. To explore an effective strategy for improving HV3 production in the future, we investigated the influence of methanol assimilation on the general gene expression in this recombinant by transcriptomic study. The results showed that methanol was partially oxidized into CO2, and the rest was converted into glycerone-P which subsequently entered into central carbon metabolism, energy metabolism, and amino acid biosynthesis. However, the later metabolic processes were almost all down-regulated. Therefore, we propose that the up-regulated central carbon metabolism, energy, and amino acid metabolism should be beneficial for methanol assimilation, which would accordingly improve the production of HV3.

scholarly journals Airpnp: Auto- and Integrated Regulation of Polynucleotide Phosphorylase

2015 ◽  
Vol 197 (24) ◽  
pp. 3748-3750 ◽  
Author(s):  
Ciarán Condon
Keyword(s):  
Gene Expression ◽  
Carbon Metabolism ◽  
Rna Degradation ◽  
Central Carbon Metabolism ◽  
Polynucleotide Phosphorylase ◽  
Link Type ◽  
Central Carbon ◽  
Integrated Regulation ◽  
Complex Regulation ◽  
Posttranscriptional Level

The properties and expression of polynucleotide phosphorylase (PNPase), capable of both RNA degradation and polymerization, have been studied for 60 years. In this issue of theJournal of Bacteriology,Park et al.(H. Park, H. Yakhnin, M. Connolly, T. Romeo, and P. Babitzke, J Bacteriol 197:3751–3759, 2015,http://dx.doi.org/10.1128/JB.00721-15) write the latest chapter on the complex regulation ofpnpgene expression involving CsrA. I describe how this new piece of the puzzle fits into the global scheme of PNPase autoregulation and how this is influenced by central carbon metabolism at both the posttranscriptional level and that of enzyme activity.

scholarly journals Quantifying absolute gene expression profiles reveals distinct regulation of central carbon metabolism genes in yeast

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rosemary Yu ◽  
Egor Vorontsov ◽  
Carina Sihlbom ◽  
Jens Nielsen
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Growth ◽  
Nitrogen Metabolism ◽  
Carbon Metabolism ◽  
Expression Profiles ◽  
Central Carbon Metabolism ◽  
Cell Growth Rate ◽  
Control Of Gene Expression ◽  
Central Carbon

In addition to controlled expression of genes by specific regulatory circuits, the abundance of proteins and transcripts can also be influenced by physiological states of the cell such as growth rate and metabolism. Here we examine the control of gene expression by growth rate and metabolism, by analyzing a multi-omics dataset consisting of absolute-quantitative abundances of the transcriptome, proteome, and amino acids in 22 steady-state yeast cultures. We find that transcription and translation are coordinately controlled by the cell growth rate via RNA polymerase II and ribosome abundance, but they are independently controlled by nitrogen metabolism via amino acid and nucleotide availabilities. Genes in central carbon metabolism, however, are distinctly regulated and do not respond to the cell growth rate or nitrogen metabolism as all other genes. Understanding these effects allows the confounding factors of growth rate and metabolism to be accounted for in gene expression profiling studies.

scholarly journals Quantifying absolute gene expression profiles reveals distinct regulation of central carbon metabolism genes in yeast

2020 ◽  
Author(s):  
Rosemary Yu ◽  
Egor Vorontsov ◽  
Carina Sihlbom ◽  
Jens Nielsen
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Growth ◽  
Carbon Metabolism ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Central Carbon Metabolism ◽  
Metabolic Parameters ◽  
Cell Growth Rate ◽  
Central Carbon

AbstractIn addition to specific regulatory circuits, gene expression is also regulated by global physiological cues such as the cell growth rate and metabolic parameters. Here we examine these global control mechanisms by analyzing an orthogonal multi-omics dataset consisting of absolute-quantitative abundances of the transcriptome, proteome, and intracellular amino acids in 22 steady-state yeast cultures. Our model indicates that transcript and protein abundance are coordinately controlled by the cell growth rate via RNA polymerase II and ribosome abundance, but are independently controlled by metabolic parameters relating to amino acid and nucleotide availability. Genes in central carbon metabolism, however, are regulated independently of these global physiological cues. Our findings can be used to augment gene expression profiling analyses in the distantly related yeast Schizosaccharomyces pombe and a human cancer cell model. Our results provide a framework to analyze gene expression profiles to gain novel biological insights, a key goal of systems biology.

scholarly journals The Transcription Factor StuA Regulates Central Carbon Metabolism, Mycotoxin Production, and Effector Gene Expression in the Wheat Pathogen Stagonospora nodorum

2010 ◽  
Vol 9 (7) ◽  
pp. 1100-1108 ◽  
Author(s):  
Simon V. S. IpCho ◽  
Kar-Chun Tan ◽  
Geraldine Koh ◽  
Joel Gummer ◽  
Richard P. Oliver ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Carbon Metabolism ◽  
Critical Role ◽  
Central Carbon Metabolism ◽  
Stagonospora Nodorum ◽  
Amino Acid Synthesis ◽  
Content Type ◽  
Central Carbon

ABSTRACT The Stagonospora nodorum StuA transcription factor gene SnStuA was identified by homology searching in the genome of the wheat pathogen Stagonospora nodorum. Gene expression analysis revealed that SnStuA transcript abundance increased throughout infection and in vitro growth to peak during sporulation. To investigate its role, the gene was deleted by homologous recombination. The growth of the resulting mutants was retarded on glucose compared to the wild-type growth, and the mutants also failed to sporulate. Glutamate as a sole carbon source restored the growth rate defect observed on glucose, although sporulation remained impaired. The SnstuA strains were essentially nonpathogenic, with only minor growth observed around the point of inoculation. The role of SnstuA was investigated using metabolomics, which revealed that this gene's product played a key role in regulating central carbon metabolism, with glycolysis, the TCA cycle, and amino acid synthesis all affected in the mutants. SnStuA was also found to positively regulate the synthesis of the mycotoxin alternariol. Gene expression studies on the recently identified effectors in Stagonospora nodorum found that SnStuA was a positive regulator of SnTox3 but was not required for the expression of ToxA. This study has uncovered a multitude of novel regulatory targets of SnStuA and has highlighted the critical role of this gene product in the pathogenicity of Stagonospora nodorum.

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