D-arabinose 5-phosphate isomerase (API)

D-arabinose 5-phosphate isomerase (API) is a critical enzyme in the biosynthetic pathway of 3-deoxy-D-manno-oct-2-ulosonic acid (KDO), a sugar residue essential for the formation of lipopolysaccharides (LPS) in almost all Gram-negative bacteria (Meredith & Woodard, 2003, J. Biol. Chem.). The enzyme catalyzes the reversible conversion between D-ribulose 5-phosphate and D-arabinose 5-phosphate, the latter being the first committed precursor for KDO synthesis (UniProt P0AF24). Because LPS is vital for the structural integrity and antibiotic resistance of the bacterial outer membrane, API is a highly attractive target for the development of novel antibacterial agents (PubMed ID: 12913008). Inhibition of this enzyme leads to the production of a truncated or absent LPS layer, significantly increasing bacterial susceptibility to the host immune system and external stressors. Since the KDO biosynthetic pathway is entirely absent in humans, targeting API offers a high degree of selectivity and minimal potential for host toxicity (Tzeng et al., 2002, J. Bacteriol.). Current research efforts focus on designing transition-state analogs and substrate mimics to overcome the therapeutic challenge of delivering polar molecules across the bacterial envelope (BRENDA EC 5.3.1.13).

Other names

Arabinose-5-phosphate isomerasePhosphoarabinose isomeraseKdsDGutQD-ribulose-5-phosphate isomerase

Inhibition of the enzymatic isomerization of D-ribulose 5-phosphate to D-arabinose 5-phosphate, thereby blocking the synthesis of 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) and disrupting lipopolysaccharide (LPS) assembly.