Monensin is a

polyether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

isolated from ''

Streptomyces cinnamonensis ''Streptomyces virginiae'' is a bacterium species from the genus of ''Streptomyces'' which has been isolated from soil.Deutsche Sammlung von Mikroorganismen und Zellkulturen]/ref> ''Streptomyces virginiae'' produces actithiazic acid, virginiamyc ...

''. It is widely used in ruminant animal feeds. The structure of monensin was first described by Agtarap et al. in 1967, and was the first polyether antibiotic to have its structure elucidated in this way. The first total synthesis of monensin was reported in 1979 by Kishi et al.

Mechanism of action

Monensin A is an ionophore related to the crown ethers with a preference to form complexes with monovalent

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

s such as: Li⁺, Na⁺, K⁺, Rb⁺, Ag⁺, and Tl⁺. Monensin A is able to transport these cations across lipid membranes of cells in an electroneutral (i.e. non-depolarizing) exchange, playing an important role as an Na⁺/H⁺

antiporter An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma memb ...

. Recent studies have shown that monensin may transport sodium ion through the membrane in both electrogenic and electroneutral manner. This approach explains ionophoric ability and in consequence antibacterial properties of not only parental monensin, but also its derivatives that do not possess carboxylic groups. It blocks intracellular protein transport, and exhibits

, antimalarial, and other biological activities. The

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

properties of monensin and its derivatives are a result of their ability to transport metal cations through cellular and subcellular

membranes A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

Uses

Monensin is used extensively in the beef and dairy industries to prevent coccidiosis, increase the production of propionic acid and prevent bloat. Furthermore, monensin, but also its derivatives monensin methyl

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

(MME), and particularly monensin decyl ester (MDE) are widely used in

ion-selective electrode An ion-selective electrode (ISE), also known as a specific ion electrode (SIE), is a transducer (or sensor) that converts the activity of a specific ion dissolved in a solution into an electrical potential. The voltage is theoretically dependent ...

s. In laboratory research, monensin is used extensively to block Golgi transport.

Toxicity

Monensin has some degree of activity on mammalian cells and thus toxicity is common. This is especially pronounced in horses, where monensin has a

median lethal dose In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the ...

1/100th that of ruminants. Accidental poisoning of equines with monensin is a well-documented occurrence which has resulted in deaths.

References

{{Nonribosomally synthesized porters Polyketide antibiotics Ionophores Carboxylic acids Spiro compounds Tetrahydrofurans