Biosynthesis of ethers: Unusual or common natural events?

Ether bonds are found in a wide variety of natural products - mainly secondary metabolites - including lipids, oxiranes, terpenoids, flavonoids, polyketides, and carbohydrate derivatives, to name some representative examples. To furnish such a biodiversity of structures, a large number of different enzymes are involved in several different biosynthetic pathways. Depending on the compound and on the (micro) environment in which the reaction is performed, ethers are produced by very different (enzymatic) reactions, thus providing an impressive display of how Nature has combined evolution and thermodynamics to be able to produce a vast number of compounds. In addition, many of these compounds possess different biological activities of pharmacological interest. Moreover, some of these ethers (i.e., epoxides) have high chemical reactivity, and can be useful starting materials for further synthetic processes. This review aims to provide an overview of the different strategies that are found in Nature for the formation of these 'bioethers'. Both fundamental and practical insights of the biosynthetic processes will be discussed.