题目: Tiacumicin Congeners with Improved Antibacterial Activity from a Halogenase-Inactivated Mutant

作者: Haibo Zhang, Xiaoxing Tian, Xiaohui Pu, Qingbo Zhang, Wenjun Zhang, and Changsheng Zhang*

刊物: Journal of Natural Products

年卷期页: 2018,81:1219-1224

摘要：Tiacumicin B (1, also known as fidaxomicin or difimicin) is a marketed drug for the treatment of Clostridium dif f icile infections. The biosynthetic pathway of 1 has been studied in Dactylosporangium aurantiacum subsp. hamdenensis NRRL 18085 and has enabled the identification of TiaM as a tailoring dihalogenase. Herein we report the isolation, structure elucidation, and bioactivity evaluation of 14 tiacumicin congeners (including 11 new ones) from the tiaM-inactivated mutant. A new tiacumicin congener, 3, with a propyl group at C-7？ of the aromatic ring was found to exhibit improved antibacterial activity.