Biomimetic synthesis of gramicidin s and analogues by enzymatic cyclization of linear precursors on solid support.
[reaction: see text] Gramicidin S is a potent decapeptide antibiotic with high hemolytic activity but is unlikely to provoke microbial resistance. Here we demonstrate that gramicidin thioesterase (GrsB TE) correctly cyclizes immobilized linear decapeptide precursors into head-to-tail products, indicating its suitability for parallel solid-phase synthesis of gramicidin analogues from linear precursors on solid support. This chemoenzymatic method will enable the optimization of the therapeutic index of the natural product to fight microbial resistance.
Department of Chemistry and Biotechnology Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Xiaoming
X
Wu
Xianzhang
X
Bu
Ka Man
KM
Wong
Weili
W
Yan
Zhihong
Z
Guo
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D040761:Biomimetic Materials; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D006096:Gramicidin / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
D000900:Anti-Bacterial Agents; D006096:Gramicidin