Photo credit: Anar Hoboken Murphy, Wiley Blackwell

Paper on hemoglobin-producing yeast cells wins prestigious prize

Tuesday 05 Apr 16
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Jens Nielsen
Chief Scientific Officer
DTU Biosustain

Contact

Anne Wärme Lykke
Communications Officer
DTU Biosustain
+45 21 12 37 70

What is the B&B Elmer Gaden Award?

  • The B&B Elmer Gaden Award is one of the most prestigious awards in biochemical engineering and is given for an excellent research paper published in Biotechnology & Bioengineering.
  •  It is named after the founder of the journal, Professor Elmer L. Gaden, who is often described as the father of biochemical engineering, because of his pioneering work on developing the technology for ensuring sufficient airing of large scale fermentation processes. This airing technology was crucial for the production of commercial penicillin in the 1940’s. 

Artificial blood is hard to produce

  • Efficient production of appropriate oxygen carriers for transfusions, for instance blood substitutes or artificial blood has been pursued for many decades. To date, several strategies have been used, from synthetic polymers to cell-free hemoglobin carriers.
  •  The recent advances in the field of metabolic engineering allow for the generation of different genetically modified organisms for the production of recombinant human hemoglobin.
  •  Even with the proper active hemoglobin at hand, there are still some obstacles before it is safe for use in humans. Hemoglobin is toxic to the body, when it is not bound to oxygen. Hence, it must be assembled with a cell-like carrier, to make the complex look and act like a red blood cell in the body.

Scientists from The Novo Nordisk Foundation Center For Biosustainability has shown that yeast cells can produce great amounts of active human hemoglobin – the proteins of red blood cells that transport oxygen. Now, the scientific paper has been granted the prestigious B&B Elmer Gaden Award.

Until recently, scientists have struggled to produce the oxygen carrying proteins of blood called hemoglobin using microbes. These proteins will allow scientists to generate blood substitutes that can prevent transfer of diseases from blood donors and enable a secure supply for blood transfusions.

"This cell line can potentially revolutionize the way we make blood for transfusions"
Professor Jens Nielsen from The Novo Nordisk Foundation Center For Biosustainability

But now, researchers from The Novo Nordisk Foundation Center For Biosustainability has shown that yeast can be engineered to produce large amounts of active human hemoglobin – a protein that can potentially save the lives of thousand of patients in need of a blood transfusion.

The research was published in the journal “Biotechnology & Bioengineering”, and the paper was awarded the 2016 B&B Elmer Gaden Award for Best Paper, which is given in recognition of an outstanding paper published in the journal in the past year.

E.coli scrapped for yeast

For decades researchers have tried to engineer the bacterium E.coli into producing hemoglobin – the protein of red blood cells responsible for carrying oxygen around in the body.

The experiments showed that E.coli can produce hemoglobin, but that the proteins were relatively unstable and had a limited ability to carry oxygen due to their bacterial origin.

Therefore, the researchers from The Novo Nordisk Foundation Center For Biosustainability decided to use yeast (Saccharomyces cerevisiae) instead. Because of yeast’s close resemblance to human cells, it should in theory be a better candidate for the production of human hemoglobin.

The scientists introduced small ring-shaped DNA-molecules (plasmids) carrying important genes for hemoglobin-production. In the first designer yeast cell lines, the yield was 4 percent hemoglobin of the total cell protein content, compared to 5 percent obtained in E.coli.

Yeast was tricked into overproducing hemoglobin

In the most recent experiments, the scientists deleted a transcription factor called HAP1, which controls the gene expression in response to the availability of specific iron-containing molecules (heme) and oxygen within the cell.

Without the HAP1, the cells produce more hemoglobin due to the lack of natural regulation. This resulted in a total yield of an impressive 7 percent of the total protein content of the yeast cells.

If putting the yeast in large scale production, using a tank of for instance 100.000 liters, the yield would be about 200 kg of active hemoglobin in 24 hours. Healthy humans have about 150 grams of haemoglobin per liter of blood, and hence this would give an amount of hemoglobin equivalent to approximately 1300 liters of blood.

“This cell line can potentially revolutionize the way we make blood for transfusions. When it is possible to produce effective oxygen carriers at a low cost in cells, it will become more attractive to use this method instead of making it chemically or to isolate hemoglobin from animal blood,” says professor Jens Nielsen, who won the prize and gave a lecture on the subject in San Diego, USA.

Further reading: 

Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae authored by José L. Martínez, Lifang Liu, Dina Petranovic and Jens Nielsen. DIO: 10.1002/bit.25347

Contact

Jens Nielsen, nielsenj@chalmers.se, tlf: +46 (0)31 772 3804

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