De Novo Biosynthesis of β-Valienamine in Engineered Streptomyces hygroscopicus 5008

详细信息    查看全文

• 作者：Li Cui ; Ying Zhu ; Xiaoqing Guan ; Zixin Deng ; Linquan Bai ; Yan Feng
• 刊名：ACS Synthetic Biology
• 出版年：2016
• 出版时间：January 15, 2016
• 年：2016
• 卷：5
• 期：1
• 页码：15-20
• 全文大小：358K
• ISSN：2161-5063

文摘

The C₇N aminocyclitol β-valienamine is a lead compound for the development of new biologically active β-glycosidase inhibitors as chemical chaperone therapeutic agents for lysosomal storage diseases. Its chemical synthesis is challenging due to the presence of multichiral centers in the structure. Herein, we took advantage of a heterogeneous aminotransferase with stereospecificity and designed a novel pathway for producing β-valienamine in Streptomyces hygroscopicus 5008, a validamycin producer. The aminotransferase BtrR from Bacillus circulans was able to convert valienone to β-valienamine with an optical purity of up to >99.9% enantiomeric excess value in vitro. When the aminotransferase gene was introduced into a mutant of S. hygroscopicus 5008 accumulating valienone, 20 mg/L of β-valienamine was produced after 96 h cultivation in shaking flasks. This work provides a powerful alternative for preparing the chiral intermediates for pharmaceutical development.