Dynamic control of gene expression in Saccharomyces cerevisiae engineered for the production of plant sesquitepene α-santalene in a fed-batch mode

2012 ◽  
Vol 14 (2) ◽  
pp. 91-103 ◽  
Author(s):  
Gionata Scalcinati ◽  
Christoph Knuf ◽  
Siavash Partow ◽  
Yun Chen ◽  
Jérôme Maury ◽  
...  
2019 ◽  
Author(s):  
Cameron J. Glasscock ◽  
John T. Lazar ◽  
Bradley W. Biggs ◽  
Jack H. Arnold ◽  
Min Kyoung Kang ◽  
...  

AbstractDynamic pathway regulation has emerged as a promising strategy in metabolic engineering for improved system productivity and yield, and continues to grow in sophistication. Bacterial stress-response promoters allow dynamic gene regulation using the host’s natural transcriptional networks, but lack the flexibility to control the expression timing and overall magnitude of pathway genes. Here, we report a strategy that uses RNA transcriptional regulators to introduce another layer of control over the output of natural stress-response promoters. This new class of gene expression cassette, called a riboregulated switchable feedback promoter (rSFP), can be modularly activated using a variety of mechanisms, from manual induction to quorum sensing. We develop and apply rSFPs to regulate a toxic cytochrome P450 enzyme in the context of a Taxol precursor biosynthesis pathway and show this leads to 2.4x fold higher titers than from the best reported strain. We envision that rSFPs will become a valuable tool for flexible and dynamic control of gene expression in metabolic engineering, protein and biologic production, and many other applications.


1992 ◽  
Vol 18 (5) ◽  
pp. 693-700 ◽  
Author(s):  
Takayuki Ohshima ◽  
Xiao-Li Zhang ◽  
Shinji Iijima ◽  
Takeshi Kobayashi ◽  
Fumio Hishinuma

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148320 ◽  
Author(s):  
Anssi Rantasalo ◽  
Elena Czeizler ◽  
Riitta Virtanen ◽  
Juho Rousu ◽  
Harri Lähdesmäki ◽  
...  

2017 ◽  
Author(s):  
Xia Wang ◽  
Pidong Li ◽  
Ryan N. Gutenkunst

AbstractDynamic control of gene expression is crucial for cellular adaptation to environmental challenges. mRNA secondary structure is known to be associated with mRNA and protein abundance, but little is known about how mRNA secondary structure affects gene expression dynamics. We report a genome-wide computational analysis of mRNA secondary structure, codon usage, and gene expression in budding yeast. We show that mRNA secondary structure combined with codon optimality regulates gene expression in multiple ways, from transcription to mRNA stability to translation. Moreover, we find that the effect of mRNA secondary structure on mRNA abundance is primarily mediated by transcription, not mRNA stability. Notably, genes with low mRNA secondary structure were substantially enriched for functions relevant to stress response, acting in the mitochondrion, endoplasmic reticulum, and ribosome. On the other hand, genes with high mRNA secondary structure were enriched for functions relevant to cellular maintenance, including macromolecular metabolism and biosynthesis. Our results suggest that mRNA secondary structure affects gene expression through coordination of multiple stages in protein biogenesis, with important consequences for stress response. The coupling of transcription to mRNA stability to translation makes concerted changes in mRNA and protein abundance possible and may amplify the effect of regulation to make quick responses to environmental variations.


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