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2.B.2 The Monensin (Monensin) Family

Monensin A and B are two polyketide antibiotics synthesized by Streptomyces cinnamonensis. They insert into membranes and exert their toxic effects by transporting monovalent ions (K+, Na+ and H+) across biological membranes in an electroneutral exchange process, thus collapsing individual ion gradients without dissipating the membrane potential. Na+ is strongly preferred to K+. Thus, Na+:H+ antiport is the favored reaction. Recently monensin has been shown to also mediate the rapid selective transport of lead (Pb2+) (Hamidinia et al., 2002).

Monensin is a lipid-soluble naturally occurring  antimicrobial. Its activity is mediated by its ability to exchange Na+ and K+ ions across the cell membrane thereby disrupting ionic gradients and altering cellular physiology. It is approved by Food and Drug Administration as a veterinary antibiotic to treat coccidiosis. Besides veterinary applications, monensin exhibits broad spectrum activities against opportunistic pathogens of humans such as bacteria, virus, fungi and parasites in both drug sensitive and resistant strains. This ionophore can selectively kill pathogens with negligible toxic effect on mammalian cells (Rajendran et al. 2018).

The generalized reaction catalyzed by monensins is:

C1+ (in) + C2+ C1+ (out) + C2+ (in)

References associated with 2.B.2 family:

Eisenman, G., G. Szabo, S.G.A. McLaughlin, and S.M. Ciani. (1973). Molecular basis for the action of macrocyclic carriers on passive ionic translocation across lipid bilayer membranes. Bioenergetics 4: 93-148. 4717529
Hamidinia, S.A., O.I. Shimelis, B. Tan, W.L. Erdahl, C.J. Chapman, G.D. Renkes, R.W. Taylor, and D.R. Pfeiffer. (2002). Monensin mediates a rapid and selective transport of Pb2+. Possible application of monensin for the treatment of Pb2+ intoxication. J. Biol. Chem. 277: 38111-38120. 12080080
Harold, F.M., K.H. Altendorf, and H. Hirata. (1974). Probing membrane transport mechanisms with ionophores. Annals N.Y. Acad. Sci. 235: 149-160. 4527943
Hutchinson, C.R. (1999). Commentary. Microbial polyketide synthases: more and more prolific. Proc. Natl. Acad. Sci. USA. 96: 3336-3338.
Liu, H.B. and K.A. Reynolds. (1999). Role of crotonyl coenzyme a reductase in determining the ratio of polyketides monensin A and monensin B produced by Streptomyces cinnamonensis. J. Bacteriol. 181: 6806-6813. 10542184
Rajendran, V., H.S. Ilamathi, S. Dutt, T.S. Lakshminarayana, and P.C. Ghosh. (2018). Chemotherapeutic Potential of Monensin as an Anti-microbial Agent. Curr Top Med Chem 18: 1976-1986. 30499391