Nitrogen-centered radicals driving unusual enzyme reactions in biosynthetic pathways

Nitrogen-centered radicals have emerged as versatile intermediates in natural product biosynthesis, playing pivotal roles in complex bond-forming and rearrangement reactions-including fragmentations, cyclizations, and dimerizations. These transformations enable the efficient construction of structurally intricate alkaloids, amino acids, cofactors, and other scaffolds that are often inaccessible via classical polar mechanisms. This review provides an overview of the enzymatic systems discovered and characterized over the past decade that harness nitrogen-centered radicals to mediate diverse biological transformations. Emphasis is placed on the enzymatic strategies for generating and precisely controlling these reactive species, with detailed discussions of their underlying mechanisms. These insights underscore the expanding role of nitrogen radical chemistry in biology and highlight its potential in the development of new biocatalytic platforms for synthetically challenging transformations.