Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. In this recent Science publication, Hartrampf et al. report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids long with over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. They demonstrated the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials displayed biophysical and enzymatic properties comparable to the biologically expressed proteins. They conclude that high-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.
Synthesis of proteins by automated flow chemistry
N. Hartrampf, A. Saebi, M. Poskus, Z. P. Gates, A. J. Callahan, A. E. Cowfer, S. Hanna, S. Antilla, C. K. Schissel, A. J. Quartararo, X. Ye, A. J. Mijalis, M. D. Simon, A. Loas, S. Liu, C. Jessen, T. E. Nielsen, B. L. Pentelute
Science 368, 980–987 (2020)