Arabinose-5-phosphate isomerase (API)

Arabinose-5-phosphate isomerase (API) is a critical enzyme in Gram-negative bacteria that catalyzes the reversible isomerization of D-ribulose 5-phosphate to D-arabinose 5-phosphate (UniProt: P0AF18). This reaction represents the first committed step in the biosynthesis of 3-deoxy-D-manno-oct-2-ulosonic acid (KDO), an essential sugar residue that anchors the lipopolysaccharide (LPS) to the lipid A moiety in the bacterial outer membrane (PubMed: 11741444). Because LPS is indispensable for the structural integrity and antibiotic resistance of most Gram-negative pathogens, API is regarded as a high-priority target for the development of novel antimicrobial agents (PubMed: 15659349). Inhibition of API leads to the production of KDO-deficient LPS, which results in growth arrest or increased sensitivity to the host immune system and other antibiotics (PubMed: 10411887). Since the KDO biosynthetic pathway is unique to bacteria and absent in humans, API inhibitors offer a potentially high therapeutic index with minimal off-target effects. Research in this area primarily involves the design of substrate analogs and transition-state mimics to block the enzyme's active site and disrupt bacterial cell wall assembly (PubMed: 16212415).

Other names

D-arabinose-5-phosphate isomerasePhosphoarabinose isomeraseKdsDGutQ

Inhibition of the first committed step of the KDO biosynthesis pathway, which prevents the assembly of essential lipopolysaccharide components in the Gram-negative bacterial outer membrane.