https://spj.science.org/doi/10.34133/research.0413
https://spj.science.org/doi/10.34133/research.0413
A research team from CAS Tianjin Institute of Industrial Biotechnology combined ancestral sequence reconstruction, reverse mutation assay, and progressive forward accumulation to identify 5 founder residues in the catalytic pocket of flavone 6-hydroxylase (F6H) and proposed a “3-point fixation” model to elucidate the functional innovation mechanisms of P450s in nature. According to this design principle of catalytic pocket, they developed a de novo diffusion model (P450Diffusion) to generate artificial P450s. Among the 17 non-natural P450s they generated, 10 designs exhibited significant F6H activity and 6 exhibited a 1.3- to 3.5-fold increase in catalytic capacity compared to the natural CYP706X1. This work explores the design principle of catalytic pockets of P450s and provides an insight into the artificial design of P450 enzymes with desired functions.
