Cofactorindependent

Cofactorindependent refers to enzymes or catalytic processes that do not require non-protein cofactors for activity. This contrasts with cofactor-dependent enzymes that rely on cofactors such as metal ions or organic molecules like NAD+, FAD, heme, biotin, or coenzyme A to enable catalysis or substrate binding. In cofatorindependent catalysis, all chemical transformation relies on the protein’s active-site architecture and the intrinsic chemistry of amino acid side chains.

Mechanisms typically involve general acid-base catalysis, formation of covalent intermediates with substrate, or precise positioning of catalytic residues to stabilize transition states. Because they do not require external cofactors, these enzymes can sometimes function in environments where cofactors are scarce or energetically costly to regenerate.

A canonical example is class I fructose-1,6-bisphosphate aldolase, which catalyzes aldol cleavage via a lysine-mediated Schiff base with the substrate and does not require metal ions or organic prosthetic groups. Other enzymes also operate without cofactors, though the vast majority of primary metabolic enzymes in cells depend on cofactors for regulation and specialization.

In research and biotechnology, cofatorindependent enzymes are of interest because they may simplify reaction design and reduce costs associated with cofactor supply or recycling. They also illustrate how protein scaffolds alone can achieve sophisticated catalytic tasks.