This article explores how metabolism influences the structural evolution of enzymes over 400 million years in Saccharomycotina yeasts. Using advanced tools like AlphaFold2, researchers analyzed thousands of enzyme structures to reveal hierarchical patterns of evolution shaped by metabolic properties across various scales, from species-wide specialization to molecular interactions. Key findings indicate that enzyme evolution is constrained by catalytic function, reaction mechanisms, interactions with small molecules, and metabolic costs, with binding sites being the most conserved and surface residues evolving most rapidly. The study highlights how factors like protein abundance, metabolic flux variability, and enzyme class dictate amino acid substitutions and cost optimization, ultimately establishing a model where enzyme structure is intimately linked to its catalytic role and metabolic environment.
References:
