AI-guided ribosome redesign trims the genetic code from 20 to 19 amino acids
A Columbia-Harvard team used AI-based protein design and AlphaFold to create an isoleucine-free ribosome in E. coli, progressively replacing the small ribosomal subunit’s genes and finally making an isoleucine-free subunit with one design that allowed growth to about 60%–70% of normal. They replaced 20 of 21 subunit genes, leaving the rplW gene as the final hurdle; after ~400 generations the strain carried 20–30 mutations but did not reintroduce isoleucine, underscoring both the potential and limits of a reduced genetic code and AI-driven design for fundamental biology.
