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AI-Designed E. coli Ribosomes Operate Without Isoleucine

AI design revealed the ribosome can tolerate losing one building block of proteins.

Overview

  • Researchers engineered an E. coli strain, called Ec19, whose ribosomal proteins were redesigned to work without the amino acid isoleucine.
  • The team achieved more than 90 percent of normal fitness and the edits held for 450 generations, showing the changes were stable.
  • They combined protein language models such as ESM2 and MSA Transformer with structure tools like AlphaFold2 and ProteinMPNN to propose and vet substitutions.
  • An earlier find‑and‑replace of isoleucine with similar amino acids left cells at about 40 percent fitness, which drove the shift to AI‑guided redesign.
  • Ec19 is not a full 19‑amino‑acid organism, and scaling this approach will likely need faster, cheaper DNA synthesis and AI models that work across whole genomes.