Genetic code expansion has tremendous potential to revolutionize peptide, protein, and protein-like therapeutics through the strategic substitution of non-canonical amino acids – or even more exotic monomers – to improve functional diversity, pharmacodynamics, produce antibody-drug conjugates, or even generate novel macrocycles. In all of these applications, yield and (especially) purity are paramount; both can be difficult to achieve without extensive optimization.
In a recent paper published in ACS Central Science, Schepartz lab graduate student Sebasthian Santiago reports that a commercial strain of Vibrio natriegens known as Vmax X2 can generate exceptional yields of soluble protein containing up to 5 non-canonical α-amino acids (ncAA), The yields obtained in Vmax X2 are up to 25X higher than commercial E. coli expression strains and more than 10X higher than two popular genomically recoded organisms (GROs). In collaboration with Amgen, Sebasthian found that proteins produced in Vmax X2 cells have significantly lower levels of mis-incorporated natural α-amino acids at the UAG-programmed position, especially in cases where the ncAA is a non-optimal substrate for the chosen orthogonal aminoacyl tRNA synthetase (aaRS). These results suggest that Vmax has tremendous untapped potential for the production of novel proteins, materials, and therapeutics.
Check out the paper: