Beta-lysine 5,6-aminomutase (5,6-LAM)

Beta-lysine 5,6-aminomutase (5,6-LAM) is a specialized isomerase enzyme that catalyzes the reversible interconversion of L-beta-lysine and 3,5-diaminohexanoate [6, 15]. It is primarily found in anaerobic bacteria, including the human gut microbiota and pathogens such as Porphyromonas gingivalis, where it facilitates the degradation of lysine for energy production [11, 13]. The enzyme is notable for its complex catalytic mechanism, which requires both pyridoxal-5'-phosphate (PLP) and adenosylcobalamin (coenzyme B12) as cofactors [4, 8]. During catalysis, the enzyme undergoes significant conformational changes to bring the cofactors into proximity, generating a 5'-deoxyadenosyl radical that initiates a 1,2-amino shift on the substrate [13]. While not present in humans, 5,6-LAM is considered a potential therapeutic target for the development of narrow-spectrum antibiotics against anaerobic infections [14, 18]. It is also of interest for the modulation of gut microbial metabolism, particularly in the context of butyrate production and intestinal health [18, 19]. Research has identified mechanism-based inhibitors, such as 4-oxalysine and 4-thia-L-lysine, which serve as tools to study its radical-mediated chemistry [13, 15]. These inhibitors provide a structural basis for the design of more potent and selective agents targeting bacterial lysine metabolism [15]. The enzyme's dependence on vitamin B12 makes it a unique model for studying radical-based enzymatic transformations [13]. Overall, 5,6-LAM represents a niche but important target in the study of microbial biochemistry and antimicrobial drug discovery [11, 14].

Other names

Beta-lysine mutaseL-beta-lysine 5,6-aminomutaseD-lysine 5,6-aminomutasekamEkamD

Radical-mediated 1,2-amino shift