Production of acetophenone C-glucosides using an engineered C-glycosyltransferase in Escherichia coli

TETRAHEDRON LETTERS

卷:59

Article

Chen, Dawei^1,2,3  Chen, Ridao^1,2,3  Xie, Kebo^1,2,3  Duan, Yangyang^1,2,3  Dai, Jungui^1,2,3 

[1] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Substance & Funct Nat Med, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Chinese Acad Med Sci, Inst Mat Med, Key Lab Biosynth Nat Prod Natl Hlth & Family Plan, Beijing 100050, Peoples R China

关键词: C-Glycosyltransferase;    Whole-cell bioconversion;    Mono-C-glucosides;    Bis-C-glucosides;    SGLT2 inhibitors;   

DOI  :  10.1016/j.tetlet.2018.04.006

来源: Elsevier

【 摘 要 】

Eight novel acetophenone mono- and bis-C-glucosides were obtained by whole cells harboring an engineered C-glycosyltransferase. Optimization of the fed-bath process improved the yield of 4a to 0.97 mg/mL with 95% conversion rate, which is 2.9-fold higher than that of the single-bath. Four mono-C-glucosides (1a-4a) exhibited potent SGLT2 inhibitory activities with IC50 values at 10(-6) M. These findings provide a cost-effective and practical synthetic strategy to produce structurally diverse and novel bioactive C-glucosides for drug discovery. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

Free