A Six-Oxidase Cascade for Tandem C-H Bond Activation Revealed by Reconstitution of Bicyclomycin Biosynthesis
| Autor: | Juan Zhao, Wei Han, Song Meng, Gong-Li Tang, Xiao-Hong Jian, Hai-Xue Pan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Cytochrome
Stereochemistry 010402 general chemistry 01 natural sciences Catalysis Mass Spectrometry Bicyclomycin chemistry.chemical_compound Biosynthesis RNA Transfer Moiety Peptide Synthases Oxidase test biology 010405 organic chemistry General Chemistry General Medicine Bridged Bicyclo Compounds Heterocyclic Piperazinedione Carbon Streptomyces 0104 chemical sciences Anti-Bacterial Agents chemistry Genes Bacterial Multigene Family biology.protein Triol Isoleucine Oxidoreductases Dimerization Chromatography Liquid Hydrogen |
| Zdroj: | Angewandte Chemie (International ed. in English). 57(3) |
| ISSN: | 1521-3773 |
| Popis: | As a commercial antibiotic, bicyclomycin (BCM) is currently the only known natural product targeting the transcription termination factor rho. It belongs to a family of highly functionalized diketopiperazine (DKP) alkaloids and bears a unique O-bridged bicyclo[4.2.2]piperazinedione ring system, a C1 triol, and terminal exo-methylene groups. We have identified and characterized the BCM biosynthetic pathway by heterologous biotransformations, in vitro biochemical assays, and one-pot enzymatic synthesis. A tRNA-dependent cyclodipeptide synthase guides the heterodimerization of leucine and isoleucine to afford the DKP precursor; subsequently, six redox enzymes, including five α-ketoglutarate/Fe2+ -dependent dioxygenases and one cytochrome P450 monooxygenase, regio- and stereoselectively install four hydroxy groups (primary, secondary, and two tertiary), an exo-methylene moiety, and a medium-sized bridged ring through the functionalization of eight unactivated C-H bonds. |
| Databáze: | OpenAIRE |
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