Corporate Banner
Satellite Banner
AgriGenomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Less Toxic Metabolites, More Chemical Product

Published: Thursday, October 31, 2013
Last Updated: Thursday, October 31, 2013
Bookmark and Share
The first dynamic regulatory system that prevents the build-up of toxic metabolites in engineered microbes has been reported.

The JBEI researchers used their system to double the production in Escherichia coli (E. coli) of amorphadiene, a precursor to the premier antimalarial drug artemisinin.

Using genome-wide transcriptional analysis, the JBEI researchers identified native regions of DNA – called “promoters” – in E. coli that respond to toxic metabolites by promoting the expression of protective genes. They then developed a system based on these promoters for regulating artificial metabolic pathways engineered into the E.coli to enable the bacterium to produce amorphadiene.

“Static regulators of toxic metabolite levels have been developed but this is the first metabolite regulator that responds to changes in microbial growth and environmental conditions,” says Jay Keasling, CEO of JBEI and ranking authority on synthetic biology, who led this research. “Control systems that can sense and respond to environmental or growth changes are needed for the optimal production of a desired chemical.”

Keasling, who also serves as Associate Laboratory Director of Biosciences at Lawrence Berkeley National Laboratory (Berkeley Lab), the lead institute in the JBEI partnership, is the corresponding author of a paper describing this research in the journal Nature Biotechnology. The paper is titled “Engineering dynamic pathway regulation using stress-response promoters.” Co-authors are Robert Dahl, Fuzhong Zhang, Jorge Alonso-Gutierrez, Edward Baidoo, Tanveer Batth, Alyssa  Redding-Johanson, Christopher Petzold, Aindrila Mukhopadhyay, Taek Soon Lee and Paul Adams.

From life-saving drugs, such as artemisinin, to sustainable, green biofuels, the metabolic engineering of microbes for the production of valuable chemicals continues to grow in importance. To date, the most productive microbial hosts have been those engineered with heterologous pathways for which they have little or no native regulation of the metabolites being expressed. However, such unregulated expression of heterologous enzymes can be toxic to the host, which can limit the production of the target chemical to well below levels that could be obtained.

“Although synthetic biology has made great strides in creating novel, dynamic genetic circuits, most control systems for heterologous metabolic pathways still rely on inducible or constitutive promoters,” Keasling says. “Approaches developed to tailor expression strength by means of promoter libraries, mRNA stability or ribosome-binding are optimized for a particular growth phase or condition in the bioreactor, however, growth and environmental conditions change during the fermentation process.”

Since the accumulation of intermediate metabolites to toxic levels in a microbe during a fermentation process can lead to a stress response, Keasling and his JBEI colleagues reasoned that it should be possible to tap a host microbe’s native stress response system when metabolites accumulate. Transcript profiling of the E.coli genome allowed them to evaluate  transcriptional response to a heterologous pathway and create a list of promoters that could be used to respond to intermediate toxicity.

“Using such promoters to regulate pathway expression in response to the toxic intermediate metabolites creates a link between the cell’s metabolic state and the expression of the metabolic pathway,” Keasling says. “This enables us to create biosensors that respond to and regulate pathway intermediates. In silico models have indicated, and we’ve demonstrated in this study that our approach can be used to improve production of a desired chemical over common inducible promoters and constitutive promoters of various strengths.”

Keasling and his colleagues believe their dynamic approach to metabolite regulation could be extended to higher organisms as well, where constitutive promot¬ers are still commonly used. This holds potential for – among other things – improving the accumulation of nutrients in food crops, or decreasing the lignin in energy crops that makes extraction of fuel sugars difficult and expensive.

“What we’re looking at are strategies that could help reduce the problems associated with feeding a larger global population or efficiently converting biomass into renewable fuels,” Keasling says.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 4,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Sugar for Biofuels: Making Do with More
Joint BioEnergy Institute researchers engineer plant cell walls to boost sugar yields for biofuels.
Tuesday, April 02, 2013
The next carbon capture tool could be new, improved grass
Miscanthus, a potential feedstock for biofuel, could pull double duty in the fight against climate change by sequestering carbon in the soil for thousands of years.
Tuesday, October 26, 2010
Scientific News
JPK NanoWizard® Applied to a Wide Range of Research
The NanoWizard® AFM from JPK is applied for interdisciplinary research at the University of South Australia for applications including smart wound healing and how plants can protect themselves from toxins.
Protein Boosts Rice Yield by 54%
Over-expression of a natural protein in rice plants led to a 54% increase in crop yield and 40% increase in nitrogen-use efficiency.
Genome of 6000-Year-Old Barley Sequenced
Researchers have successfully sequenced the genome of Chalcolithic barley grains for the first time.
Flowers Arrange Themselves for Bees
Study suggests plants can maximise their chances of reproduction by taking advantage of how insects move when they gather nectar.
Improving Wheat Crops in the Field
Agrii, RAGT and the University of Nottingham are developing better disease management and yield production in wheat crops using ASD FieldSpec Handheld 2 portable spectroradiometers.
Unravelling the Roots of Insect’s Waterproof Coating
Researchers have identified the genes that control cuticular lipid production in Drosophila, by performing an RNAi screen and using Direct Analysis in Real Time and GC-MS.
Structural link to Brain Cell Death in Alzheimer's
Study reveals multiple new leads for pursuing potential Alzheimer's treatments
Disentangling the Plant Microbiome
Study says breeding plants, to feed a growing global population, with more beneficial bacteria is far from simple.
Cellular Origin of Skin Cancer Identified
Scientists have identified ‘cell of origin’ in the most common form of skin cancer, and followed the process that leads to tumour growth.
How Plants Sense Electric Fields
An international group of researchers has identified the sensor plants use to sense electric fields. The voltage sensor discovery could contribute to the understanding of how the Ebola virus enters human cells.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!