Bacteria are the original inventors of the assembly line principle, producing a wide variety of natural products through non-ribosomal peptide synthetases (NRPS). These enzyme complexes have become essential tools for synthetic biology, with many important drugs, such as antibiotics, derived from them.
Helge Bode's research team at the Max Planck Institute for Terrestrial has discovered new "fusion sites" in NRPS, enabling faster and more targeted drug development. By examining protein evolution, the team identified areas where enzyme components naturally combine to create new "assembly lines" for the production of required active compounds.
For the study published in Science, the team analyzed several tens of thousands of enzymes and combined bioinformatic analysis with laboratory experiments to verify the predicted target sites. They successfully found a new "fusion point" for the targeted production of functional NRPS hybrids, even combining sequences from different organisms, such as bacteria and fungi.
"Research in both synthetic biology and evolutionary biochemistry has made enormous progress in recent years," said Bode. "The key advantage of our approach is that we are using evolutionary processes that have proven themselves over millions of years. Our evolution-inspired fusion sites are more versatile and have higher success rates.”