Scientists from Columbia University, the Massachusetts Institute of Technology, and Harvard University have engineered a modified strain of E. coli bacteria using AI and protein engineering. This strain operates with only 19 amino acids by eliminating isoleucine from its ribosome, marking the first synthetic organism to function without one of the 20 universal amino acids essential to life.
The Groundbreaking Experiment
A study published in Science outlines how researchers targeted the ribosome, the cellular machinery that assembles proteins. They replaced all 382 isoleucine residues in the ribosome with alternative amino acids predicted by AI protein language models. These models generated novel protein sequences that preserved ribosomal function, designs humans might not have conceived.
Isoleucine was selected due to its chemical similarity to leucine and valine, making it the most viable candidate for removal. Of 50 initial E. coli strains with isoleucine substitutions, 18 grew normally. Researchers then integrated 21 rewritten ribosomal proteins into a single strain, which grew successfully after refinements, though more slowly than unmodified versions.
This achievement is unprecedented. While prior efforts expanded genetic codes by adding amino acids to bacteria and yeast, removing one has never been accomplished until now.
Implications for Biology and Beyond
Harris Wang, a systems and synthetic biologist at Columbia University, described the feat as “almost the hardest thing you could think about, because it’s the biggest, most complicated protein complex.” The results demonstrate that core biological systems can endure major genetic disruptions.
The discovery bolsters theories that early life forms relied on fewer than 20 amino acids, reshaping evolutionary perspectives. It also opens doors to synthetic organisms tailored for medicine, healthcare, and extreme environments like space habitats, where full amino acid availability may be limited.
Modified organisms could depend on unique chemistries absent in nature, enhancing biological containment for safer applications.
