MINT ENZYMES · Microbial Expression Platform for Membrane Integrated Enzymes
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2012-07-01 → 2016-06-30
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Мембранните протеини и ензими се проучват чрез промяна на генетичния код в микроорганизми, за да се произведат по-ефективно. Това помага за създаването на нови лекарства и синтеза на медицински важни вещества.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Microbial Expression Platform for Membrane Integrated Enzymes
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. Membrane integrated (MINT) proteins and enzymes perform crucial tasks in living organisms and are prime drug targets, but are difficult to produce in their fully functional state due to their hydrophobic character. Our long-term goal is to learn how the DNA code affects folding of membrane proteins and how to recode them for better production in microorganisms. In the first two years of the MINT enzymes project we have successfully optimized the expression of two membrane transporters by introducing synonymous mutations on the 5´end o their coding sequences. Additionally we have constructed variants of tRNA over-expressing plasmids for studying the effect of codon usage in microbial cell factories. Finally we engineered E. coli for high-level production of precursors of the medically important diterpene forskolin. In the last two years of the project we have contributed with the development of synthetic biology tools for cell factory engineering.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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
Оригинален текст от CORDIS (на английски).
Участници
- DANMARKS TEKNISKE UNIVERSITET · Kongens LyngbyКоординаторДания
Връзки
Данни: CORDIS, © Европейски съюз