We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Enzymatic C−H Oxidation-Amidation Cascade in the Production of Natural and Unnatural Thiotetronate Antibiotics with Potentiated Bioactivity.
- Authors
Li, Jie; Tang, Xiaoyu; Awakawa, Takayoshi; Moore, Bradley S.
- Abstract
The selective activation of unreactive hydrocarbons by biosynthetic enzymes has inspired new synthetic methods in C−H bond activation. Herein, we report the unprecedented two-step biosynthetic conversion of thiotetromycin to thiotetroamide C involving the tandem oxidation and amidation of an unreactive ethyl group. We detail the genetic and biochemical basis for the terminal amidation in thiotetroamide C biosynthesis, which involves a uniquely adapted cytochrome P450-amidotransferase enzyme pair and highlights the first oxidation-amidation enzymatic cascade reaction leading to the selective formation of a primary amide group from a chemically inert alkyl group. Motivated by the ten-fold increase in antibiotic potency of thiotetroamide C ascribed to the acetamide group and the unusual enzymology involved, we enzymatically interrogated diverse thiolactomycin analogues and prepared an unnatural thiotetroamide C analogue with potentiated bioactivity compared to the parent molecule.
- Subjects
HYDROCARBONS; ENZYMOLOGY; AMIDES; ALKYL group; HYDROXYLATION; AMINATION kinetics
- Publication
Angewandte Chemie, 2017, Vol 129, Issue 40, p12402
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201705239