Now in Chem Sci! 🎉
We investigated how #enzymes in the #nonribosomal #biosynthesis of life-saving #peptide #antibiotics can be engineered.
Assuming that #promiscuity serves as a springboard for #evolution, we measured the specificity profiles of hundreds of mutants. The results revealed remarkable shifts in substrate specificity in multiple directions, highlighting the evolutionary potential of these enzymes and leading the way for engineering antibiotic biosynthesis.

https://doi.org/10.1039/D6SC00250A

#DirectedEvolution is a powerful method but has not been easy to do with gigantic #nonribosomal biocatalysts that make important #antibiotics. We have developed a #microfluidics screen that uses liposomes as sensors for membrane active peptides. Bacteria are grown in tiny droplets. If they make gramicidin S, the sensor liposomes burst, liberate calcein, and generate fluorescence. This was tested for screening mutants and may become a useful tool for directed evolution. https://www.biorxiv.org/content/10.1101/2023.01.13.523969v1