scholarly journals Aspergillus: A Powerful Protein Production Platform

Catalysts ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1064 ◽  
Author(s):  
Fani Ntana ◽  
Uffe Hasbro Mortensen ◽  
Catherine Sarazin ◽  
Rainer Figge
Keyword(s):  
Recombinant Protein ◽  
Protein Production ◽  
Production Efficiency ◽  
Aspergillus Species ◽  
Industrial Biotechnology ◽  
Cell Factories ◽  
Production Platform ◽  
Heterologous Expression Systems ◽  
Protease Deficient ◽  
Key Steps

Aspergilli have been widely used in the production of organic acids, enzymes, and secondary metabolites for almost a century. Today, several GRAS (generally recognized as safe) Aspergillus species hold a central role in the field of industrial biotechnology with multiple profitable applications. Since the 1990s, research has focused on the use of Aspergillus species in the development of cell factories for the production of recombinant proteins mainly due to their natively high secretion capacity. Advances in the Aspergillus-specific molecular toolkit and combination of several engineering strategies (e.g., protease-deficient strains and fusions to carrier proteins) resulted in strains able to generate high titers of recombinant fungal proteins. However, the production of non-fungal proteins appears to still be inefficient due to bottlenecks in fungal expression and secretion machinery. After a brief overview of the different heterologous expression systems currently available, this review focuses on the filamentous fungi belonging to the genus Aspergillus and their use in recombinant protein production. We describe key steps in protein synthesis and secretion that may limit production efficiency in Aspergillus systems and present genetic engineering approaches and bioprocessing strategies that have been adopted in order to improve recombinant protein titers and expand the potential of Aspergilli as competitive production platforms.

scholarly journals Special Issue: Recombinant Protein Expression in Microorganisms

2019 ◽  
Vol 7 (9) ◽  
pp. 355
Author(s):  
Trygve Brautaset ◽  
Svein Valla
Keyword(s):  
Recombinant Protein ◽  
Protein Expression ◽  
Recombinant Protein Expression ◽  
Sustainable Production ◽  
Industrial Biotechnology ◽  
Special Issue ◽  
Cell Factories ◽  
Wide Range

Microorganisms are widely used in industrial biotechnology as cell factories for the sustainable production of a wide range of compounds and chemicals [...]

scholarly journals Engineering the protein secretory pathway of Saccharomyces cerevisiae enables improved protein production

2018 ◽  
Vol 115 (47) ◽  
pp. E11025-E11032 ◽  
Author(s):  
Mingtao Huang ◽  
Guokun Wang ◽  
Jiufu Qin ◽  
Dina Petranovic ◽  
Jens Nielsen
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Recombinant Protein ◽  
Protein Secretion ◽  
Protein Production ◽  
Secretory Pathway ◽  
Synergistic Effects ◽  
Production Capacity ◽  
Market Demand ◽  
Protein Retention ◽  
Cell Factories

Baker’s yeast Saccharomyces cerevisiae is one of the most important and widely used cell factories for recombinant protein production. Many strategies have been applied to engineer this yeast for improving its protein production capacity, but productivity is still relatively low, and with increasing market demand, it is important to identify new gene targets, especially targets that have synergistic effects with previously identified targets. Despite improved protein production, previous studies rarely focused on processes associated with intracellular protein retention. Here we identified genetic modifications involved in the secretory and trafficking pathways, the histone deacetylase complex, and carbohydrate metabolic processes as targets for improving protein secretion in yeast. Especially modifications on the endosome-to-Golgi trafficking was found to effectively reduce protein retention besides increasing protein secretion. Through combinatorial genetic manipulations of several of the newly identified gene targets, we enhanced the protein production capacity of yeast by more than fivefold, and the best engineered strains could produce 2.5 g/L of a fungal α-amylase with less than 10% of the recombinant protein retained within the cells, using fed-batch cultivation.

scholarly journals Bioreactor-Scale Strategies for the Production of Recombinant Protein in the Yeast Yarrowia lipolytica

2019 ◽  
Vol 7 (2) ◽  
pp. 40 ◽  
Author(s):  
Marie Vandermies ◽  
Patrick Fickers
Keyword(s):  
Recombinant Protein ◽  
Yarrowia Lipolytica ◽  
Recombinant Protein Production ◽  
Protein Production ◽  
Genetic Manipulation ◽  
Research Field ◽  
Cell Factory ◽  
Cell Factories ◽  
A Cell ◽  
High Level

Recombinant protein production represents a multibillion-dollar market. Therefore, it constitutes an important research field both in academia and industry. The use of yeast as a cell factory presents several advantages such as ease of genetic manipulation, growth at high cell density, and the possibility of post-translational modifications. Yarrowia lipolytica is considered as one of the most attractive hosts due to its ability to metabolize raw substrate, to express genes at a high level, and to secrete protein in large amounts. In recent years, several reviews have been dedicated to genetic tools developed for this purpose. Though the construction of efficient cell factories for recombinant protein synthesis is important, the development of an efficient process for recombinant protein production in a bioreactor constitutes an equally vital aspect. Indeed, a sports car cannot drive fast on a gravel road. The aim of this review is to provide a comprehensive snapshot of process tools to consider for recombinant protein production in bioreactor using Y. lipolytica as a cell factory, in order to facilitate the decision-making for future strain and process engineering.

Continuous bleed recycling significantly increases recombinant protein production yield in perfusion cell cultures

2021 ◽  
Vol 169 ◽  
pp. 107966
Author(s):  
Jean-Marc Bielser ◽  
Mathieu Aeby ◽  
Stefania Caso ◽  
Anaïs Roulet ◽  
Hervé Broly ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Cell Cultures ◽  
Recombinant Protein Production ◽  
Protein Production ◽  
Production Yield
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