Oxygen-independent enzymatic dearomatization of homocyclic aromatic compounds

Covering: 1995 up to the end of 2025Homocyclic aromatic compounds (HAC) represent the second most abundant class of natural and anthropogenic products. Their biodegradation is central to the global carbon cycle and the bioremediation of aromatic pollutants. A key step in this process is enzymatic dearomatization, historically attributed exclusively to oxygen-dependent mono- or dioxygenases. However, over the past three decades, a growing diversity of oxygen-independent dearomatizing reductases has been identified. These enzymes act either on partially activated di- or trihydroxybenzenes and trihydroxynaphthalenes with meta-oriented hydroxyl groups, or on coenzyme A (CoA) thioesters of carboxylated HAC, converting aromatic substrates into cyclic dienes. Class I and II benzoyl-CoA reductases catalyze Birch-like reductions via radical intermediates at metal cofactors, with low-potential electrons supplied either through ATP-dependent electron transfer (class I) or flavin-based electron bifurcation (class II), whereas 2-naphthoyl-CoA reductase appears independent of an electron-activation system. An alternative, non-redox dearomatization mechanism has been identified in S-adenosyl-L-methionine-dependent methyltransferases involved in the anaerobic bacterial estrogen-to-androgen conversion, as well as in polyketide tailoring. Together, these findings reveal a broad enzymatic repertoire for overcoming arene resonance stabilization under anoxic conditions. Beyond their ecological significance, these pathways provide mechanistically diverse routes and opportunities for biocatalysis and the sustainable synthesis of valuable chemical building blocks.