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De Novo Biosynthesis of β‑Valienamine in Engineered Streptomyces hygroscopicus 5008
journal contributionposted on 2016-01-15, 00:00 authored by Li Cui, Ying Zhu, Xiaoqing Guan, Zixin Deng, Linquan Bai, Yan Feng
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.
valienamineEngineered Streptomyces hygroscopicus 5008aminotransferase genechiral intermediatesaminotransferase BtrRlysosomal storage diseaseschemical synthesischemical chaperonevalienone96 h cultivation7NDe Novo Biosynthesishygroscopicus 5008Bacillus circulansmultichiral centersnovel pathwayvalidamycin producer