QGEM is looking into the rational design of novel adenylation domains, which are responsible for activating the correct amino acid to add. We are using molecular dynamics coupled with machine learning to score and evaluate in silico mutations. Through mutating the adenylation domain sequence to allow it to overcome its stringent specificity for its natural amino acid substrate, our goal is to be able to incorporate novel or synthetic amino acids into nonribosomal peptides. This will significantly expand the variety of compounds we can synthesize using NRPS.
Figure 3. The adenylation domain (A-domain), shown along with the other main domains of NRPS (PCP and C), is primarily responsible for recognition of the amino acid being incorporated into the nonribosomal peptide through adenylation. By evaluating in silico mutations of the A-domain active site, we hope to engineer A-domains to recognize and incorporate novel/synthetic amino acids not commonly found in nature. This potential of NRPS allows for us to envision using NRPS systems to develop a library of novel pharmaceutical drugs for the future. To learn more about the essential NRPS domains, visit the NRPS section on our About Synthetic Biology Page!
1. Koumoutsi, Alexandra. Domain catalyzed reactions. 2007. Functional genome analysis of the plant-growth promoting bacterium Bacillus amyloliquefaciens strain FZB42; characterizing its production and regulation of nonribosomal peptide synthesis. EDoc Hu-Berlin. Web. 17 Jun. 2016.