The discovery of biologically active small molecules by cultivation and isolation of natural products from bacteria, fungi, and plants has long been considered a green and sustainable approach to the development of new therapuetic agents. Now that the easily accessible natural molecules have been fully exploited, humanity must now search precious organisms, genetically engineer microbes to produce new structures, or utilize time-consuming chemical synthesis to produce new functional compounds. In order to provide an alternative approach to the generation and screening of large number of small organic molecules, we have recently introduced <i>synthetic fermentation </i>as a method that allows complex, biologically active organic molecules to be “grown” from small molecule building blocks by mixing them under aqueous conditions. This technology produces small mixtures of structurally diverse molecules – including unprotected functional groups – suitable for testing without any purification or use of toxic reagents. The underlying chemistry is made possible by chemoselective reactions that proceed in water and new approaches to controlled oligomerization. This talk with describe our development of the chemistry and synthesis of the requisite monomers, the application of synthetic fermentation to the discovery of antiviral and antibacterial compounds, and the implications of the ability to generate millions of molecules under safe, aqueous conditions without the need for toxic reagents or organic solvents.<br/>

Synthetic fermentation of bioactive peptides in water without reagents or organisms

250th National Meeting (2015)

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