Transcriptional regulatory proteins in central carbon metabolism ofPichia pastorisandSaccharomyces cerevisiae

Kalender, Ozge
Çalık, Pınar
System-wide interactions in living cells and discovery of the diverse roles of transcriptional regulatory proteins that are mediator proteins with catalytic domains and regulatory subunits and transcription factors in the cellular pathways have become crucial for understanding the cellular response to environmental conditions. This review provides information for future metabolic engineering strategies through analyses on the highly interconnected regulatory networks inSaccharomyces cerevisiaeandPichia pastorisand identifying their components. We discuss the current knowledge on the carbon catabolite repression (CCR) mechanism, interconnecting regulatory system of the central metabolic pathways that regulate cell metabolism based on nutrient availability in the industrial yeasts. The regulatory proteins and their functions in the CCR signalling pathways in both yeasts are presented and discussed. We highlight the importance of metabolic signalling networks by signifying ways on how effective engineering strategies can be designed for generating novel regulatory circuits, furthermore to activate pathways that reconfigure the network architecture. We summarize the evidence that engineering of multilayer regulation is needed for directed evolution of the cellular network by putting the transcriptional control into a new perspective for the regulation of central carbon metabolism of the industrial yeasts; furthermore, we suggest research directions that may help to enhance production of recombinant products in the widely used, creatively engineered, but relatively less studiedP. pastoristhrough de novo metabolic engineering strategies based on the discovery of components of signalling pathways in CCR metabolism.


Transcriptional engineering of the glyceraldehyde-3-phosphate dehydrogenase promoter for improved heterologous protein production in Pichia pastoris
Ata, Ozge; Prielhofer, Roland; Gasser, Brigitte; Mattanovich, Diethard; Çalık, Pınar (2017-10-01)
The constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (P-GAP), which is one of the benchmark promoters of Pichia pastoris, was analyzed in terms of putative transcription factor binding sites. We constructed a synthetic library with distinct regulatory properties through deletion and duplication of these putative transcription factor binding sites and selected transcription factor (TF) genes were overexpressed or deleted to understand their roles on heterologous protein production. Using enhanc...
Transcriptional engineering of GAP promoter for improved recombinant protein production by Pichia pastoris
Ata, Özge; Çalık, Pınar; Mattanovich, Diethard; Department of Biotechnology (2017)
The objective of this PhD thesis is to enhance the expression strength of glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP) for improved recombinant protein (r-protein) production through modifying the transcription factors (TF) that regulate the functioning of PGAP by transcriptional engineering. PGAP was analyzed in terms of putative TF binding sites. A synthetic library was constructed with distinct regulatory properties through deletion and duplication of these putative transcription factor bindi...
Expression Analysis of TaNAC69-1 and TtNAMB-2, Wheat NAC Family Transcription Factor Genes Under Abiotic Stress Conditions in Durum Wheat (Triticum turgidum)
Baloglu, Mehmet Cengiz; Oz, Mehmet Tufan; Öktem, Hüseyin Avni; Yücel, Ayşe Meral (2012-10-01)
NAC-type plant-specific transcription factor genes encode proteins that play important roles in abiotic stress responses, as well as regulation of plant development. In the current study, expression profiles of wheat NAC-type transcription factor genes, TaNAC69-1 and TtNAMB-2, were examined under drought, salt, cold, and heat stress conditions in wheat. Based on reverse transcription quantitative PCR results, TaNAC69-1 was strongly expressed under drought, salinity, and high-temperature stress conditions. C...
In-silico determination of Pichia pastoris signal peptides for extracellular recombinant protein production
Massahi, Aslan; Çalık, Pınar (2015-01-07)
In-silico identified novel secretory signal peptides (SPs) are required in vivo to achieve efficient transfer or to prevent other cellular proteins from interfering with the process in extracellular recombinant protein (r-protein) production. 56 endogenous and exogenous secretory SPs, have been used or having the potential to be used in Pichia pastoris for r-protein secretion, were analyzed in-silico using the softwares namely SignalP4.1, Phobius, WolfPsort0.2, ProP1.0, and NetNGlyc1.0. Among the predicted ...
Transcriptional regulatory network refinement and quantification through kinetic modeling, gene expression microarray data and information theory
Sayyed-Ahmad, Abdallah; Tuncay, Kağan; Ortoleva, Peter J. (Springer Science and Business Media LLC, 2007-01-23)
Background: Gene expression microarray and other multiplex data hold promise for addressing the challenges of cellular complexity, refined diagnoses and the discovery of well-targeted treatments. A new approach to the construction and quantification of transcriptional regulatory networks (TRNs) is presented that integrates gene expression microarray data and cell modeling through information theory. Given a partial TRN and time series data, a probability density is constructed that is a functional of the ti...
Citation Formats
O. Kalender and P. Çalık, “Transcriptional regulatory proteins in central carbon metabolism ofPichia pastorisandSaccharomyces cerevisiae,” APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, pp. 7273–7311, 2020, Accessed: 00, 2020. [Online]. Available: