"A core cellular machine can operate with only 19 of the standard 20 amino acids."
Scientists redesign E. coli ribosome to function without isoleucine
Researchers at Columbia University have engineered the ribosome of Escherichia coli to operate without the amino acid isoleucine—a breakthrough published today in Science.
The core finding
The ribosomal complex, a crucial cellular machine composed of over 50 proteins and catalytic RNA that translates genetic instructions into proteins, can now function using only 19 of the 20 standard amino acids.
Overcoming earlier failures
Synthetic biologist Harris Wang, who led the research, noted that early attempts to replace isoleucine with chemically similar amino acids failed, with fewer than half of modified proteins retaining their function.
The role of AI
The team turned to artificial intelligence tools, including AlphaFold and protein language models, to identify non-intuitive substitutions that enabled the ribosome's proteins to remain functional without isoleucine.
Next steps
Wang plans to extend this approach to the entire proteome—potentially reshaping how we understand and engineer the fundamental building blocks of life.