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Microbial Expression Platform for Membrane Integrated Enzymes

Objective

We wish to explore how and why the architecture of the DNA code for membrane proteins vary between kingdoms and affect protein production under different growth conditions - with an unprecedented systematic approach. At the core of biotechnology is heterologous expression of proteins, i.e. to transfer genes into foreign hosts like microorganisms for protein production. One of the key challenges in protein production relates to the degeneracy of the genetic code. Genetic information flows from DNA via RNA into proteins, but the code is degenerate because different DNA/RNA-nucleotide sequences can be translated into the same protein sequence. In the DNA and RNA code, three nucleotides (a codon) are translated into one amino acid residue, and amino acids can be encoded by up to six different “synonymous” codons. Substantial evidence, from studies of soluble proteins, points to a role for this “deeper layer” of the genetic code in the proper timing of co-translational protein folding. For example, regions rich in rare codons may slow down translation to allow time for folding of specific secondary structures. However, since codon usage is not conserved like the universal genetic code, protein-folding information hidden in the DNA code is difficult to transfer from one organism to another. As a result, heterologous expression often leads to misfolded, non-functional proteins. Very limited experimental evidence exist on the connection between codon usage and production of functionally active proteins and in the case of membrane-integrated protein, no such systematic studies have been performed. The knowledge gained will be exploited to engineer new scaffolds for microbial factories. Successful designs will be a novel, invaluable tool in molecular biology and may spawn future solutions for converting from a fossil fuel-based to a bio-based industrial society

Call for proposal

FP7-PEOPLE-2011-CIG
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Coordinator

DANMARKS TEKNISKE UNIVERSITET
Address
Anker Engelundsvej 1 Bygning 101 A
2800 Kgs Lyngby
Denmark
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 100 000
Administrative Contact
Susanne Plougheld Winther (Ms.)