Significance The versatility of promiscuous enzymes plays a key role in the evolution of catalysts. This work addresses the molecular mechanism of repurposing a promiscuous enzyme by laboratory evolution and reveals that mutations distinct from the catalytic machinery reshaped the active site. Evolution fine-tuned binding of a previously disfavored Michaelis complex (E·S), repositioning the promiscuous substrate to enable better charge offset during leaving group departure in the transition state. The functional transition relies on maintaining the reactivity of existing catalytic groups in a permissive active-site architecture, able to accommodate multiple substrate binding modes, without requiring changes in conformational dynamics. Such a parsimonious route to higher efficiency illustrates a molecular scenario in which catalytic promiscuity facilitates short adaptive pathways of evolution.