Exploring the mechanism of compromised thermostability of aromatic L-amino acid decarboxylase from Bacillus atrophaeus through comparative molecular dynamics simulations

As an excellent biocatalyst, aromatic L-amino acid decarboxylase from Bacillus atrophaeus (BaAADC) catalyzes the production of various vital aromatic biogenic amines. However, its weak heat resistance makes BaAADC un-suitable for industrial production. Here, we generated the three-dimensional structure of BaAADC and used molecular dynamics simulations to investigate the dynamic behavior of BaAADC at different temperatures (303-343 K) to investigate the association between its thermal stability and internal residues. We have shown that the natural structure of BaAADC is altered at high temperatures, with more striking alterations in secondary structure at the active site, fewer internal hydrogen bonding, and greater amino acid flexibility in the active pocket. Based on the root mean square fluctuations, the residues ASN46, GLU54, ALA113, ASP324, VAL329, and GLU332 were confirmed to be the most flexible. Salt bridge analysis revealed ion pairs ASP182-ARG197, ASP299-ARG347, GLU121-ARG344, GLU326-ARG316, GLU337-ARG316, GLU341-ARG347, and GLU470-ARG427 were partially responsible for the inactivation of BaAADC at high temperatures. In addition, strate-gies to improve the thermostability of BaAADC were discussed. This research might provide light on the development and modification of thermostable BaAADC.