Enzyme design moves past amino acids: structures now yield E. coli-ready coding sequences, and two Cel5E sites gain heat tolerance and activity together
Generative enzyme design has mostly optimized at the amino acid level, rarely accounting for coding sequences and host expression at once. EZPro-Fit places protein 3D structure, coding sequences and taxonomic information in one generative framework, pretrained on thermophilic microbial data and fine-tuned on highly expressed E. coli genes, so it generates host-adapted coding sequences directly from structure. On the industrial endoglucanase Cel5E, its variants N291D and D259E raised both melting temperature and catalytic activity in experiments.