Development of catalytic covalent biomimetic acyltransferases

Abstract

Thioesters are ubiquitous in many biochemical pathways throughout the cell, often being used as precursors for amide bond formation. Thioesters are more reactive and less stable than their (oxygen) ester counterparts but are still stable enough to hydrolysis to be used for reactions in aqueous systems. For example, the coenzyme acetyl coenzyme A (AcCoA) holds acetate equivalents as thioesters, then transfers them as part of multiple catabolic systems. Thioester acyl transfer is also key in protein ubiquination, polyketide synthesis, glutathione biosynthesis, and intein splicing, among many other pathways. In this work, we looked at intercepting these reactive thioester intermediates, utilizing both inteins and small molecule catalysts to modify proteins.