Biomimetic Thioesters as Probes for Enzymatic Assembly Lines: Synthesis, Applications, and Challenges

摘要: Thioesters play essential roles in many biosynthetic pathways to fatty acids, esters, polyketides, and non-ribosomal peptides. Coenzyme A (CoA) related phosphopantetheine thioesters are typically employed as activated acyl units for diverse C-C, C-O, C-N coupling reactions. To study control these enzymatic assembly lines in vitro in vivo structurally simplified analogs such N-acetylcysteamine (NAC) have been developed. This review gives an overview on experimental strategies enabled by synthetic NAC thioesters, the elucidation of complex enzyme mechanisms well precursor-directed biosynthesis mutasynthesis. The also summarizes protocols protection group access versatile tools, which reactive often unstable compounds. In addition, alternative thioester mimics presented that can be used protein tags or suicide inhibitors crosslinking off-loading probes elucidate polyketide intermediates.