Carbon metabolism influenced for promoters and temperature used in the heterologous protein production using Pichia pastoris yeast

Zepeda, Andrea B.; Pessoa, Adalberto; Farías, Jorge G.

doi:10.1016/j.bjm.2018.03.010

Cited by 31 publications

(28 citation statements)

References 70 publications

(164 reference statements)

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“…It's acknowledged that low cultivation temperature can lead to a higher foreign protein production level in microorganism (Jahic et al, 2003;Mattanovich et al, 2004). The advantages of low cultivation temperature include the favorable effects on energy metabolism, protein folding and secretion, protein degradation and aggregation in recombinant microorganism cells (Georgiou and Valax, 1996;Cassland and Jonsson, 1999;Li et al, 2001;Zepeda et al, 2018), moreover, on the economical efficiency in industrial fermentation production. Sometimes, a low cultivation temperature is even a requisite condition for the production of some particular proteins, such as psychrophilic and mesophilic proteins (Vigentini et al, 2006).…”

Section: Low Temperaturementioning

confidence: 99%

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Enhanced Recombinant Protein Production Under Special Environmental Stress

Chen

Liang

2021

Front. Microbiol.

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Regardless of bacteria or eukaryotic microorganism hosts, improving their ability to express heterologous proteins is always a goal worthy of elaborate study. In addition to traditional methods including intracellular synthesis process regulation and extracellular environment optimization, some special or extreme conditions can also be employed to create an enhancing effect on heterologous protein production. In this review, we summarize some extreme environmental factors used for the improvement of heterologous protein expression, including low temperature, hypoxia, microgravity and high osmolality. The applications of these strategies are elaborated with examples of well-documented studies. We also demonstrated the confirmed or hypothetical mechanisms of environment stress affecting the host behaviors. In addition, multi-omics techniques driving the stress-responsive research for construction of efficient microbial cell factories are also prospected at the end.

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Section: Low Temperaturementioning

confidence: 99%

“…The lower growth temperature was employed, the higher ratio of the right conformations in inclusion bodies was observed (de Groot and Ventura, 2006). Furthermore, a low cultivation temperature can result in a reduced extracellular proteolysis (Jahic et al, 2003;Torija et al, 2003;Zepeda et al, 2018).…”

Section: Low Temperaturementioning

confidence: 99%

Enhanced Recombinant Protein Production Under Special Environmental Stress

Chen

Liang

2021

Front. Microbiol.

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“…K. phaffii can utilize glucose, glycerol, sorbitol, methanol, ethanol, L-rhamnose, and acetate as carbon source ( Riley et al, 2016 ). A comprehensive overview of the carbon sources and their diauxism is given by Zepeda et al (2018) .…”

Section: Growth Behavior: Carbon Sources Methanol Assimilation and mentioning

confidence: 99%

Komagataella phaffii as Emerging Model Organism in Fundamental Research

et al. 2021

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Komagataella phaffii (Pichia pastoris) is one of the most extensively applied yeast species in pharmaceutical and biotechnological industries, and, therefore, also called the biotech yeast. However, thanks to more advanced strain engineering techniques, it recently started to gain attention as model organism in fundamental research. So far, the most studied model yeast is its distant cousin, Saccharomyces cerevisiae. While these data are of great importance, they limit our knowledge to one organism only. Since the divergence of the two species 250 million years ago, K. phaffii appears to have evolved less rapidly than S. cerevisiae, which is why it remains more characteristic of the common ancient yeast ancestors and shares more features with metazoan cells. This makes K. phaffii a valuable model organism for research on eukaryotic molecular cell biology, a potential we are only beginning to fully exploit. As methylotrophic yeast, K. phaffii has the intriguing property of being able to efficiently assimilate methanol as a sole source of carbon and energy. Therefore, major efforts have been made using K. phaffii as model organism to study methanol assimilation, peroxisome biogenesis and pexophagy. Other research topics covered in this review range from yeast genetics including mating and sporulation behavior to other cellular processes such as protein secretion, lipid biosynthesis and cell wall biogenesis. In this review article, we compare data obtained from K. phaffii with S. cerevisiae and other yeasts whenever relevant, elucidate major differences, and, most importantly, highlight the big potential of using K. phaffii in fundamental research.

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“…), the cultivation conditions (pH, temperature), and the bioprocess strategy (specific growth rate of biomass etc.) (Marx et al 2006 ; Emmerstorfer et al 2014 ; Looser et al 2015 ; Barrero et al 2018 ; Gidijala et al 2018 ; Zepeda et al 2018 ; Duan et al 2019 ; Fischer and Glieder 2019 ; Liu et al 2019 ; Naranjo et al 2019 ) (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 97%

Engineering of the unfolded protein response pathway in Pichia pastoris: enhancing production of secreted recombinant proteins

Raschmanová

Weninger

Knejzlı́k

et al. 2021

Appl Microbiol Biotechnol

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Folding and processing of proteins in the endoplasmic reticulum (ER) are major impediments in the production and secretion of proteins from Pichia pastoris (Komagataella sp.). Overexpression of recombinant genes can overwhelm the innate secretory machinery of the P. pastoris cell, and incorrectly folded proteins may accumulate inside the ER. To restore proper protein folding, the cell naturally triggers an unfolded protein response (UPR) pathway, which upregulates the expression of genes coding for chaperones and other folding-assisting proteins (e.g., Kar2p, Pdi1, Ero1p) via the transcription activator Hac1p. Unfolded/misfolded proteins that cannot be repaired are degraded via the ER-associated degradation (ERAD) pathway, which decreases productivity. Co-expression of selected UPR genes, along with the recombinant gene of interest, is a common approach to enhance the production of properly folded, secreted proteins. Such an approach, however, is not always successful and sometimes, protein productivity decreases because of an unbalanced UPR. This review summarizes successful chaperone co-expression strategies in P. pastoris that are specifically related to overproduction of foreign proteins and the UPR. In addition, it illustrates possible negative effects on the cell’s physiology and productivity resulting from genetic engineering of the UPR pathway. We have focused on Pichia’s potential for commercial production of valuable proteins and we aim to optimize molecular designs so that production strains can be tailored to suit a specific heterologous product. Key points • Chaperones co-expressed with recombinant genes affect productivity in P. pastoris. • Enhanced UPR may impair strain physiology and promote protein degradation. • Gene copy number of the target gene and the chaperone determine the secretion rate.

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Carbon metabolism influenced for promoters and temperature used in the heterologous protein production using Pichia pastoris yeast

Cited by 31 publications

References 70 publications

Enhanced Recombinant Protein Production Under Special Environmental Stress

Enhanced Recombinant Protein Production Under Special Environmental Stress

Komagataella phaffii as Emerging Model Organism in Fundamental Research

Engineering of the unfolded protein response pathway in Pichia pastoris: enhancing production of secreted recombinant proteins

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