nonB12dependent

NonB12dependent, often written as non-B12-dependent, is a term used in biochemistry and molecular biology to describe enzymes or metabolic steps that do not require cobalamin (vitamin B12) as a cofactor. The distinction contrasts with B12-dependent enzymes, which rely on cobalamin for catalytic activity.

A prominent example is methionine synthase, which exists in two forms. The B12-dependent form, MetH, uses cobalamin to transfer a methyl group from a donor to homocysteine. The B12-independent form, MetE, operates without B12 and uses a different mechanism to catalyze the same overall conversion—methylation of homocysteine to form methionine—typically employing 5-methyl-tetrahydrofolate as the methyl donor and a zinc-containing active site. MetE is often less efficient and more sensitive to cellular zinc availability than MetH, but it provides a crucial alternative in environments where cobalamin is scarce or unavailable.

Non-B12dependent enzymes and pathways are widespread in bacteria and archaea, contributing to metabolic flexibility under varying vitamin B12 supply. The term is commonly used in genomic and biochemical annotations to indicate the absence of a B12 dependency, or to describe paralogous enzymes where one variant is B12-dependent and another is not. Regulation often reflects micronutrient availability: organisms may express non-B12dependent forms when cobalamin is limited, switching to B12-dependent forms when B12 is abundant.

Applications include metabolic engineering and industrial microbiology, where introducing or maintaining non-B12dependent pathways can reduce the need for B12 supplementation. See also vitamin B12, cobalamin, and methionine synthase (MetH and MetE).