EU-funded researchers have demonstrated the feasibility of bioengineering microbial strains in a controlled manner, a fundamental scientific breakthrough that has significant potential for drug development and biotechnology. The project was also instrumental in establishing a new scientific discipline - xenobiology.
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The basic chemical composition of complex living organisms is actually relatively simple, and is based on a few key compounds. Researchers working on the EU-funded METACODE project have taken advantage of this fact to modify the composition of certain existing bacteria in order to include additional amino acid building blocks.
The concept behind the project is that these bioengineered organisms will enable scientists and pharmaceutical researchers to mass-produce protein and peptide-based products with completely new chemical functionalities, opening the door to potential new drugs and treatments. Peptide-based drugs are of great interest to pharmaceutical companies as they are both highly effective and relatively safe. Around 140 peptide-based therapeutic drugs are currently being evaluated in clinical trials.
The project has significantly added to this field of research by successfully creating and demonstrating several reactions absent from nature. “These engineered bacteria are able to perform reactions that do not exist in living organisms,” explains project coordinator Nediljko Budisa from the Berlin Institute of Technology.
“Their unique properties can be exploited in biotechnology applications, for example, for generating novel peptide antibiotics. On the other hand, this technology is also the first step in the creation of synthetic life, which should be genetically and metabolically so far away from that found in nature that it cannot survive outside of laboratory conditions.”
For example, the project team successfully ‘engineered’ E. coli bacteria to produce peptides that they would not otherwise produce in nature. “In this way, we succeeded in ‘teaching’ E. coli cells to synthesise these building blocks on their own,” says Budisa. “This breakthrough represents a solid basis for the design of bacterial strains with altered genetic codes, which could lead to the creation of synthetic organisms. We believe that biodiversity created in this way will represent an important technology."
Such ‘synthetic cell factories’ can also be used to produce a novel generation of synthetic protein/peptide-based antimicrobial products.
Engineering living systems
The discovery of the mechanisms of DNA, the molecule that carries most of the genetic instructions used in the development, functioning and reproduction of all known living organisms, has enabled scientists to move from simply analysing organisms to actually starting to engineer living systems. Advances in genetic programming open the door to producing a whole new range of substances.
“Modern genetic engineers aim to build living systems – like engineers build machines – in order to create artificial biodiversity that can produce virtually every imaginable medically or industrially interesting substance,” explains Budisa. “The METACODE research philosophy has been based on the assumption that artificial biodiversity represents an important technology for the future, with living cells (mainly microbes) functioning as small programmable production units.”
Before completion in November 2015, the METACODE project showed the scientific community that the mass production of tailored protein-based anti-microbial products – achieved through genetically engineered microbial strains – is now feasible.
A new frontier
The project was instrumental in helping to establish the new scientific discipline of ‘xenobiology’. This combination of chemical synthesis and synthetic biology could lead to enhanced biopolymer engineering and pathogen resistance, and address fundamental issues such as understanding the origin of life itself.