Use of tRNA in Natural Product Biosynthesis

Recent years have seen the discovery of several roles of tRNA and tRNA synthetases in processes other than ribosomal protein biosynthesis. These functions include the use of aminoacylated tRNA in natural product biosynthesis, such as the pathways to valanimycin,  cyclodipeptides, and pacidamycin. This presentation will discuss the use of aminoacylated tRNA in the biosynthesis of phosphonate natural products such as dehydrophos, a Trojan horse type antibiotic that results in peptidase-mediated release of methyl acetylphosphonate (MAP), a potent inhibitor of pyruvate dehydrogenase. The substrate specificity of the Gcn5-related N-acetyltransferases that fashion the peptide bonds in dehydrophos will be discussed.