para-Quinone methides in natural product biosynthesis.

Covering: up to 2025para-Quinone methides (p-QMs) are highly reactive Michael acceptors with broad applications in organic synthesis, drug development, and materials science. Nature ingeniously harnesses these intermediates for diverse biochemical processes, ranging from melanization to the biosynthesis of bioactive natural products. While some natural products incorporate stable p-QM moieties, most p-QMs are transient, serving as pivotal intermediates in various metabolic pathways. This highlight examines p-QM-mediated enzymatic transformations in natural product biosynthesis, emphasizing catalytic mechanisms, substrate flexibility, and engineering potential. Understanding these biosynthetic strategies would advance enzyme discovery, inspire biomimetic synthesis, and guide rational enzyme design efforts.