Semi-Synthetic Bacteria Produce Exotic Proteins and Unnatural Amino Acids

All of Earth’s natural life forms store information using a four-letter genetic code consisting of the nucleotides deoxyadenosine (dA), deoxyguanosine (dG), deoxycytidine (dC), and deoxythymidine (dT). Within the DNA double helix, dA pairs with dT, and dG with dC, to form the “rungs” of the DNA ladder. 

Recently, researchers have made synthetic nucleotides that can pair up with each other. When they placed these unnatural nucleotides into genes, bacteria could replicate the DNA and convert the sequences into RNA and then proteins that contained unconventional amino acids. However, bacteria often cannot use these synthetic sequences as efficiently as the natural ones. Therefore, Lingjun Li, Floyd Romesberg and colleagues wanted to optimize the unnatural base pairs to improve protein production.

The researchers tested different combinations of unnatural base pairs in E. coli and observed which ones were replicated most efficiently and produced the highest levels of a protein. Some of the synthetic base pairs had been tested before, whereas others were new variations. The team then used these optimized base pairs to demonstrate, for the first time, a semi-synthetic organism that could make a protein containing multiple unnatural amino acids.

The authors acknowledge funding from the National Institutes of Health, the National Science Foundation,Boehringer Ingelheim Fonds, NASA Exobiology and Henan Normal University.

Contacts and sources:
American Chemical Society

Citation: Optimization of Replication, Transcription, and Translation in a Semi-Synthetic Organism.
Aaron W. Feldman, Vivian T. Dien, Rebekah J. Karadeema, Emil C. Fischer, Yanbo You, Brooke A. Anderson, Ramanarayanan Krishnamurthy, Jason S. Chen, Lingjun Li, Floyd E. Romesberg. Journal of the American Chemical Society, 2019; 141 (27): 10644 DOI: 10.1021/jacs.9b02075