6,7-dimethyl-8-ribityllumazine synthase (Aquifex aeolicus) (AaLS)

Lumazine synthase from the hyperthermophilic bacterium Aquifex aeolicus (AaLS) is an enzyme that catalyzes the penultimate step in the biosynthesis of riboflavin (vitamin B2) (UniProt O66840). Specifically, it facilitates the condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione with 3,4-dihydroxy-2-butanone 4-phosphate to form 6,7-dimethyl-8-ribityllumazine (Fischer et al., 2004). Structurally, AaLS is characterized by its ability to self-assemble into a highly stable, 60-subunit icosahedral capsid with a diameter of approximately 15 nm (Zhang et al., 1998). Because the riboflavin biosynthetic pathway is essential for many pathogenic bacteria and fungi but absent in humans, lumazine synthase is a significant target for the development of narrow-spectrum and broad-spectrum antimicrobial agents (Fischer et al., 2004). Beyond its enzymatic role, the robust and symmetrical structure of AaLS has led to its widespread use as a nanoparticle scaffold in vaccine engineering, notably for the multivalent display of antigens like the HIV-1 eOD-GT8 immunogen to improve B-cell activation (Jardine et al., 2013). Consequently, it serves both as a template for drug design and a critical component in modern immunotherapeutic delivery systems.

Other names

RibHLumazine synthase6,7-dimethyl-8-ribityllumazine synthaseAaLS

Competitive inhibition of the riboflavin biosynthetic pathway, preventing the production of essential flavin cofactors in microorganisms.