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Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae

Lifang Liu (Institutionen för kemi- och bioteknik, Systembiologi) ; José Luis Martinez Ruiz (Institutionen för kemi- och bioteknik, Systembiologi) ; Zihe Liu (Institutionen för kemi- och bioteknik, Systembiologi) ; Dina Petranovic (Institutionen för kemi- och bioteknik, Systembiologi) ; Jens B. Nielsen (Institutionen för kemi- och bioteknik, Systembiologi)
Metabolic Engineering (1096-7176). Vol. 21 (2014), p. 9-16.
[Artikel, refereegranskad vetenskaplig]

Due to limitations associated with whole blood for transfusions (antigen compatibility, transmission of infections, supply and storage), the use of cell-free hemoglobin as an oxygen carrier substitute has been in the center of research interest for decades. Human hemoglobin has previously been synthesized in yeast, however the challenge is to balance the expression of the two different globin subunits, as well as the supply of the prosthetic heme required for obtaining the active hemoglobin (alpha(2)beta(2)). In this work we evaluated the expression of different combinations of alpha and beta peptides and combined this with metabolic engineering of the heme biosynthetic pathway. Through evaluation of several different strategies we showed that engineering the biosynthesis pathway can substantially increase the heme level in yeast cells, and this resulted in a significant enhancement of human hemoglobin production. Besides demonstration of improved hemoglobin production our work demonstrates a novel strategy for improving the production of complex proteins, especially multimers with a prosthetic group. Crown Copyright (C) 2013 Published by Elsevier Inc. on behalf of International Metabolic Engineering Society. All rights reserved.

Nyckelord: Human hentoglobin, Heine biosynthesis, Prosthetic group, Protein production, Saccharomyces cerevisiae



Denna post skapades 2014-01-31. Senast ändrad 2014-11-06.
CPL Pubid: 193303

 

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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Systembiologi (2008-2014)

Ämnesområden

Annan medicinsk bioteknologi

Chalmers infrastruktur

 


Projekt

Denna publikation är ett resultat av följande projekt:


Industrial Systems Biology of Yeast and A. oryzae (INSYSBIO) (EC/FP7/247013)