期刊
METABOLIC ENGINEERING
卷 21, 期 -, 页码 9-16出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2013.10.010
关键词
Human hentoglobin; Heine biosynthesis; Prosthetic group; Protein production; Saccharomyces cerevisiae
资金
- European Research Council ERC project INSYSBIO [247013]
- Novo Nordisk Foundation
- Chalmers Foundation
- Knut and Alice Wallenberg Foundation
- Novo Nordisk Fonden [NNF10CC1016517] Funding Source: researchfish
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.
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