METACODE

Code-engineered new-to-nature microbial cell factories for novel and safety enhanced bio-production

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'The concept of METACODE is to preform genetic code engineering in microbial strains with parallel recruitment of novel bio-orthogonal chemistries for mass production of desired protein/peptide based products. In combination with computational and classical chemical synthetic approaches as well as chemo-informatics, enzyme guided evolution, synthetic metabolism, and directed evolution of microbial strains, artificial industrial microbial strains will be designed. This will enable the access to genetically robust and safe strains with added/novel functionalities and topologies from renewable resources. These strains will be characterized with alternative reading of the genetic code (genetic firewall) and with predetermined chemistries (metathesis), as well as necessary robustness for efficient industrial use.'

Introduzione (Teaser)

Enhancing the chemical repertoire of life would lead to novel molecules with parameters that could be adapted for various fermentative production processes. European scientists have realised this scenario by integrating artificial amino acids into the cellular machinery of microorganisms to augment bio-synthetic pathways with non-natural chemistries.

Descrizione progetto (Article)

Despite the complexity of living organisms, their chemical composition is relatively simple and is organised on a surprisingly limited set of chemistries.

If we were able to interfere with the chemistry of life, we would essentially be able to make synthetic mechanisms that carry desirable chemical functionalities and reactions.

Scientists of the EU-funded 'Code-engineered new-to-nature microbial cell factories for novel and safety enhanced bio-production' (http://www.meta-code.eu/ (METACODE)) project believe that the most promising route to achieve this is to modify existing organisms to include amino acid building blocks beyond the canonical 20. Scientists plan to perform genetic code engineering in microbial strains in parallel with novel bio-orthogonal chemistries.

This would lead to mass production of desired protein/peptide-based products with new chemical functionalities and give new dimensions to existing biocatalysis.

METACODE-generated engineered bacterial clones constitute a genetic firewall. As these clones read the genetic code in an alternative manner to natural bacteria, they will be unable to horizontally transfer their genetic material to natural bacteria. Additionally, they will be able to perform enzyme-catalysed metathesis reactions that do not exist in living organisms. This unique property will be exploited in biotechnology applications, for example, for generating artificial metalloenzymes and novel peptide antibiotics.

To incorporate non-canonical amino acids into growing polypeptide chains, the consortium had to design a strategy for re-assigning the genetic code to these amino acids. To this end, they set up an automated system to perform directed evolution of Escherichia coli strains to free low-usage sense codons and non-sense codons and re-assign them to non-canonical amino acids. This 'genetic code emancipation' would expand ribosomal peptide/protein biogenesis and give rise to novel peptides with broad biological, chemical and physical properties.

The METACODE project proved the feasibility of directed evolution of microbial strains in a controlled manner. This represents a fundamental scientific breakthrough in the field and has extraordinary potential for drug development and biotechnology.