AI Article Synopsis
Article Abstract
Background: The methylotrophic yeast Pichia pastoris is a well-studied host organism for recombinant protein production, which is usually regulated either by a constitutive promoter (e.g. promoter of glyceraldehyde-3-phosphate dehydrogenase; P) or an inducible promoter (e.g. promoter of alcohol oxidase 1; P). Both promoter systems have several advantages and disadvantages; with one of the main disadvantages being their lack of tunability. Various novel promoter systems, which are either inducible or de-repressed, allowing higher degrees of freedom, have been reported. Recently, bi-directional promoter systems in P. pastoris with two promoter systems regulating recombinant expression of one or more genes were developed. In this study, we introduce a novel bi-directional promoter system combining a modified catalase promoter system (P; derepressible and inducible) and the traditional P, allowing tunable recombinant protein production.
Results: We characterized a recombinant P. pastoris strain, carrying the novel bi-directional promoter system, during growth and production in three dynamic bioreactor cultivations. We cloned the model enzyme cellobiohydralase downstream of either promoter and applied different feeding strategies to determine the physiological boundaries of the strain. We succeeded in demonstrating tunability of recombinant protein production solely in response to the different feeding strategies and identified a mixed feed regime allowing highest productivity.
Conclusion: In this feasibility study, we present the first controlled bioreactor experiments with a recombinant P. pastoris strain carrying a novel bi-directional promotor combination of a catalase promoter variant (P) and the traditional P. We demonstrated that this bi-directional promoter system allows tunable recombinant protein expression only in response to the available C-sources. This bi-directional promoter system offers a high degree of freedom for bioprocess design and development, making bi-directional promoters in P. pastoris highly attractive for recombinant protein production.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598003 | PMC |
| http://dx.doi.org/10.1186/s12934-017-0768-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.
Cell Oncol (Dordr)
December 2024
Gene Regulation and Diseases Lab, College of Life Science and Technology, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, 430070, PR China.
Article Synopsis
- The regulation of steroid hormone receptors (SHRs) is essential for understanding how breast cancer progresses, particularly through their impact on gene transcription and chromatin remodeling.
- The review focuses on the roles of androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) in influencing estrogen receptor (ER)-mediated transcription and highlights their dual roles in either promoting or inhibiting gene expression.
- It also discusses four mechanisms of enhancer reprogramming and suggests that combining SHR modulating therapies with current endocrine treatments could enhance the effectiveness of therapies for ER-positive breast cancer.
SRSF2 safeguards efficient transcription of DNA damage and repair genes.
Cell Rep
November 2024
Division of Mechanisms Regulating Gene Expression, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address:
The serine-/arginine-rich splicing factor 2 (SRSF2) plays pivotal roles in pre-mRNA processing and gene transcription. Recurrent mutations, particularly a proline-to-histidine substitution at position 95 (P95H), are common in neoplastic diseases. Here, we assess SRSF2's diverse functions in squamous cell carcinoma.
View Article and Find Full Text PDFIntroduction: GWAS have identified multiple regions that confer risk for juvenile idiopathic arthritis (JIA). However, identifying the single nucleotide polymorphisms (SNPs) that drive disease risk is impeded by the SNPs' that identify risk loci being in linkage disequilibrium (LD) with hundreds of other SNPs. Since the causal SNPs remain unknown, it is difficult to identify target genes and use genetic information to inform patient care.
View Article and Find Full Text PDFThe non-canonically organized members of MIR395 gene family in Brassica juncea are associated with developmentally regulated, sulfate-stress responsive bidirectional promoters that exhibit orientation-dependent differential transcriptional activity.
Plant Sci
November 2024
Department of Botany, University of Delhi, Delhi 110007, India. Electronic address:
Several MICRORNA genes belonging to same family or different families are often found in homologous or non-homologous clusters. Among the various classes, head-to-head arranged genes form one of the largest categories of non-canonically organized genes. Such head-to-head arranged, non-canonically organized genes possibly share cis-regulatory region with the intergenic sequence having the potential to function as bi-directional promoter (BDP).
View Article and Find Full Text PDFBreaking the Passivation Effect for MnO Catalysts in Li-S Batteries by Anion-Cation Doping.
Angew Chem Int Ed Engl
November 2024
Joint Key Laboratory of the Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China.
Transition metal oxides (TMOs) are recognized as high-efficiency electrocatalyst systems for restraining the shuttle effect in lithium-sulfur (Li-S) batteries, owing to their robust adsorption capabilities for polysulfides. However, the sluggish catalytic conversion of LiS redox and severe passivation effect of TMOs exacerbate polysulfide shuttling and reduce the cyclability of Li-S batteries, which significantly hinders the development of TMOs electrocatalysts. Here, through the anion-cation doping approach, dual incorporation of phosphorus and molybdenum into MnO (P,Mo-MnO) was engineered, demonstrating effective mitigation of the passivation effect and allowing for the simultaneous immobilization of polysulfides and rapid redox kinetics of LiS.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!