Researchers from Columbia University, the Massachusetts Institute of Technology, and Harvard University have successfully created a strain of E. coli with just 19 amino acids by removing isoleucine from the ribosome. This marks the first known organism to possess fewer than 20 of the universal amino acids. The findings were published in a study in the journal Science and represent a significant advancement in synthetic biology and the investigation of life’s origins.
The study suggests that early life may have utilized fewer amino acids than modern organisms. Previously, scientists theorized this possibility, but had not demonstrated it in practice. The decision to remove isoleucine was based on its chemical similarity to leucine and valine, making it the most replaceable amino acid.
Researchers modified the ribosome, which assembles proteins, by substituting the 382 isoleucine building blocks while maintaining its functional integrity. This approach is innovative, as past efforts in genetic modification have focused solely on adding amino acids rather than removing them.
The experimental design involved AI protein language models to predict potential substitutes for isoleucine and analyze combinations rapidly. Out of 50 E. coli strains created, 18 were able to grow normally despite the absence of isoleucine. The subsequent phase involved combining 21 rewritten ribosomal proteins into one strain of E. coli, which showed slower growth than unmodified strains.
Harris Wang, a systems and synthetic biologist at Columbia University, acknowledged the complexity of completely eliminating an amino acid from the ribosome, describing it as “almost the hardest thing you could think about.”
The research indicates that core biological systems can tolerate significant genetic disruptions, supporting theories that simpler forms of life may exist or may have existed. Furthermore, it opens possibilities for constructing synthetic organisms tailored for specialized medical and healthcare applications.
The findings may lead to the development of organisms that depend on unconventional chemistries, enhancing biological containment. In the future, AI-assisted genetic modification could also facilitate the design of life forms suited for extreme environments, such as space habitats, where not all amino acids might be available.
