2.B.14 The Lasalocid A or X-537A Ionophore (Lasalocid) Family

Lasalocid A or X-537A is a carboxylic polyether antibacterial (particularly Gram-positive bacteria) and antifungal agent which is produced by strains of Streptomyces lasaliensis. It is a feed additive called bovatec.  Lasalocid A is able to form neutral complexes with monovalent and divalent cations and transport them through lipid bilayer membranes.  For divalent cations, the selectivity has been reported to be Ba²⁺ > Ca²⁺ > Sr²⁺, and transport possibly occurs in exchange for K⁺ in intact animal cells.  It also transports Mg²⁺ and Na⁺, and is thus much less specific that A23187 (calcimycin; TC# 2.B.11) which is primarily specific for divalent cations.  It can also transport fairly large organic cations such as dopamine (Ito et al. 1978; Eanes and Costa 1983). 

Formation of a cation inclusion complex stabilizes the cyclic conformer, even in relatively polar solvents. These observations suggest a scenario for carboxylic ionophore-mediated transmembrane monovalent cation transport. The cation encounters an acyclic ionophore at the membrane interface where it ion pairs to the terminal carboxylate moiety, initiating formation of a lipophilic, cyclic cation inclusion complex. The complex, no longer constrained to the polar interface, diffuses across the membrane interior to the opposite face. There it reequilibrates with the polar environment, the ionophore reassuming the low energy, acyclic conformation and concomitantly releasing the enclosed cation. The free, acyclic ionophore is then confined to the opposite polar interface where it awaits the capture of a new cation to complete its catalytic transport cycle (Painter et al. 1982).