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Coupling gene regulatory patterns to bioprocess conditions to optimize synthetic metabolic modules for improved sesquiterpene production in yeast

Overview of attention for article published in Biotechnology for Biofuels and Bioproducts, February 2017
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  • Above-average Attention Score compared to outputs of the same age (62nd percentile)
  • Above-average Attention Score compared to outputs of the same age and source (53rd percentile)

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Title
Coupling gene regulatory patterns to bioprocess conditions to optimize synthetic metabolic modules for improved sesquiterpene production in yeast
Published in
Biotechnology for Biofuels and Bioproducts, February 2017
DOI 10.1186/s13068-017-0728-x
Pubmed ID
Authors

Bingyin Peng, Manuel R. Plan, Alexander Carpenter, Lars K. Nielsen, Claudia E. Vickers

Abstract

Assembly of heterologous metabolic pathways is commonly required to generate microbial cell factories for industrial production of both commodity chemicals (including biofuels) and high-value chemicals. Promoter-mediated transcriptional regulation coordinates the expression of the individual components of these heterologous pathways. Expression patterns vary during culture as conditions change, and this can influence yeast physiology and productivity in both positive and negative ways. Well-characterized strategies are required for matching transcriptional regulation with desired output across changing culture conditions. Here, constitutive and inducible regulatory mechanisms were examined to optimize synthetic isoprenoid metabolic pathway modules for production of trans-nerolidol, an acyclic sesquiterpene alcohol, in yeast. The choice of regulatory system significantly affected physiological features (growth and productivity) over batch cultivation. Use of constitutive promoters resulted in poor growth during the exponential phase. Delaying expression of the assembled metabolic modules using the copper-inducible CUP1 promoter resulted in a 1.6-fold increase in the exponential-phase growth rate and a twofold increase in productivity in the post-exponential phase. However, repeated use of the CUP1 promoter in multiple expression cassettes resulted in genetic instability. A diauxie-inducible expression system, based on an engineered GAL regulatory circuit and a set of four different GAL promoters, was characterized and employed to assemble nerolidol synthetic metabolic modules. Nerolidol production was further improved by 60% to 392 mg L(-1) using this approach. Various carbon source systems were investigated in batch/fed-batch cultivation to regulate induction through the GAL system; final nerolidol titres of 4-5.5 g L(-1) were achieved, depending on the conditions. Direct comparison of different transcriptional regulatory mechanisms clearly demonstrated that coupling the output strength to the fermentation stage is important to optimize the growth fitness and overall productivities of engineered cells in industrially relevant processes. Applying different well-characterized promoters with the same induction behaviour mitigates against the risks of homologous sequence-mediated genetic instability. Using these approaches, we significantly improved sesquiterpene production in yeast.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 100 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 100 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 21%
Researcher 20 20%
Student > Bachelor 10 10%
Other 9 9%
Student > Master 8 8%
Other 9 9%
Unknown 23 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 34 34%
Agricultural and Biological Sciences 21 21%
Chemistry 7 7%
Engineering 3 3%
Pharmacology, Toxicology and Pharmaceutical Science 2 2%
Other 7 7%
Unknown 26 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 December 2022.
All research outputs
#7,962,193
of 25,382,440 outputs
Outputs from Biotechnology for Biofuels and Bioproducts
#537
of 1,578 outputs
Outputs of similar age
#119,467
of 323,958 outputs
Outputs of similar age from Biotechnology for Biofuels and Bioproducts
#23
of 49 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 1,578 research outputs from this source. They receive a mean Attention Score of 4.9. This one has gotten more attention than average, scoring higher than 64% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 323,958 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.