They Removed One of Life's 20 Essential Amino Acids from Bacteria, and It Survived 450 Generations

Key Points:

• Researchers engineered a strain of E. coli bacteria with extensive genetic modifications that replaced isoleucine with valine or leucine in 21 ribosomal proteins, demonstrating that key parts of the protein synthesis machinery can function with a reduced amino acid set.
• The modified bacteria remained alive and reproduced for over 450 generations, though they grew more slowly and still required isoleucine in most of their genome, indicating the experiment did not create a fully 19-amino-acid organism.
• Artificial intelligence protein language models played a crucial role in designing nonintuitive ribosomal protein sequences that compensated for the absence of isoleucine, enabling the bacteria's survival despite substantial genetic alterations.
• This research provides evidence supporting the feasibility of life with fewer than the standard 20 amino acids and offers an experimental framework to explore how early life might have operated before the modern genetic code was established.
• The study, published in Science, represents the largest targeted sequence changes to date in a living organism’s protein synthesis system, highlighting potential evolutionary flexibility in the amino acid alphabet.