Rational strain engineering interventions to enhance cellulase secretion by Saccharomyces cerevisiae

2017 ◽  
Vol 12 (1) ◽  
pp. 108-124 ◽  
Author(s):  
Heinrich Kroukamp ◽  
Riaan den Haan ◽  
John‐Henry van Zyl ◽  
Willem Heber van Zyl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Strain Engineering ◽  
Cellulase Secretion

scholarly journals Different Routes of Protein Folding Contribute to Improved Protein Production in Saccharomyces cerevisiae

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Qi Qi ◽  
Feiran Li ◽  
Rosemary Yu ◽  
Martin K. M. Engqvist ◽  
Verena Siewers ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Folding ◽  
Recombinant Protein ◽  
Recombinant Protein Production ◽  
Protein Production ◽  
Strain Engineering ◽  
Folding Pathway ◽  
Original Strain ◽  
Precision Control ◽  
Folding Process

ABSTRACT Protein folding is often considered the flux controlling process in protein synthesis and secretion. Here, two previously isolated Saccharomyces cerevisiae strains with increased α-amylase productivity were analyzed in chemostat cultures at different dilution rates using multi-omics data. Based on the analysis, we identified different routes of the protein folding pathway to improve protein production. In the first strain, the increased abundance of proteins working on the folding process, coordinated with upregulated glycogen metabolism and trehalose metabolism, helped increase α-amylase productivity 1.95-fold compared to the level in the original strain in chemostat culture at a dilution rate of 0.2/h. The second strain further strengthened the folding precision to improve protein production. More precise folding helps the cell improve protein production efficiency and reduce the expenditure of energy on the handling of misfolded proteins. As calculated using an enzyme-constrained genome-scale metabolic model, the second strain had an increased productivity of 2.36-fold with lower energy expenditure than that of the original under the same condition. Further study revealed that the regulation of N-glycans played an important role in the folding precision control and that overexpression of the glucosidase Cwh41p can significantly improve protein production, especially for the strains with improved folding capacity but lower folding precision. Our findings elucidated in detail the mechanisms in two strains having improved protein productivity and thereby provided novel insights for industrial recombinant protein production as well as demonstrating how multi-omics analysis can be used for identification of novel strain-engineering targets. IMPORTANCE Protein folding plays an important role in protein maturation and secretion. In recombinant protein production, many studies have focused on the folding pathway to improve productivity. Here, we identified two different routes for improving protein production by yeast. We found that improving folding precision is a better strategy. Dysfunction of this process is also associated with several aberrant protein-associated human diseases. Here, our findings about the role of glucosidase Cwh41p in the precision control system and the characterization of the strain with a more precise folding process could contribute to the development of novel therapeutic strategies.

scholarly journals Metabolic Engineering of Wine Strains of Saccharomyces cerevisiae

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 964
Author(s):  
Mikhail A. Eldarov ◽  
Andrey V. Mardanov
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Metabolic Engineering ◽  
Wine Yeast ◽  
Strain Engineering ◽  
Starter Cultures ◽  
Detailed Knowledge ◽  
Wine Quality ◽  
Wine Strain ◽  
Natural Isolates ◽  
Genomic Editing

Modern industrial winemaking is based on the use of starter cultures of specialized wine strains of Saccharomyces cerevisiae yeast. Commercial wine strains have a number of advantages over natural isolates, and it is their use that guarantees the stability and reproducibility of industrial winemaking technologies. For the highly competitive wine market with new demands for improved wine quality, it has become increasingly critical to develop new wine strains and winemaking technologies. Novel opportunities for precise wine strain engineering based on detailed knowledge of the molecular nature of a particular trait or phenotype have recently emerged due to the rapid progress in genomic and “postgenomic” studies with wine yeast strains. The review summarizes the current achievements of the metabolic engineering of wine yeast, the results of recent studies and the prospects for the application of genomic editing technologies for improving wine S. cerevisiae strains.

scholarly journals Enhanced Production of a Plant Monoterpene by Overexpression of the 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Catalytic Domain in Saccharomyces cerevisiae

2010 ◽  
Vol 76 (19) ◽  
pp. 6449-6454 ◽  
Author(s):  
Juan Rico ◽  
Ester Pardo ◽  
Margarita Orejas
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Coenzyme A ◽  
Catalytic Domain ◽  
Laboratory Strain ◽  
Strain Engineering ◽  
Enhanced Production ◽  
Wine Strain ◽  
Coa Reductase ◽  
Rate Limiting ◽  
Coenzyme A Reductase

ABSTRACT Linalool production was evaluated in different Saccharomyces cerevisiae strains expressing the Clarkia breweri linalool synthase gene (LIS). The wine strain T73 was shown to produce higher levels of linalool than conventional laboratory strains (i.e., almost three times the amount). The performance of this strain was further enhanced by manipulating the endogenous mevalonate (MVA) pathway: deregulated overexpression of the rate-limiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) doubled linalool production. In a haploid laboratory strain, engineering of this key step also improved linalool yield.

Strain engineering of Saccharomyces cerevisiae for enhanced xylose metabolism

2013 ◽  
Vol 31 (6) ◽  
pp. 851-861 ◽  
Author(s):  
Soo Rin Kim ◽  
Yong-Cheol Park ◽  
Yong-Su Jin ◽  
Jin-Ho Seo
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Strain Engineering ◽  
Xylose Metabolism

Overexpression of native PSE1 and SOD1 in Saccharomyces cerevisiae improved heterologous cellulase secretion

2013 ◽  
Vol 102 ◽  
pp. 150-156 ◽  
Author(s):  
Heinrich Kroukamp ◽  
Riaan den Haan ◽  
Niël van Wyk ◽  
Willem H. van Zyl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cellulase Secretion
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