title: De Novo Biosynthesis of β-Valienamine in Engineered Streptomyces hygroscopicus 5008.
abstract: 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.
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, and Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, and Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, and Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, and Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, and Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Linquan
authors.initials: L
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, and Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
mesh_terms: D053898:Biosynthetic Pathways; D002851:Chromatography, High Pressure Liquid; D053138:Cyclohexenes; D006595:Hexosamines / Q000096:biosynthesis*; D007294:Inositol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D007700:Kinetics; D060847:Metabolic Engineering; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D013302:Streptomyces / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism
chemical_list: D053138:Cyclohexenes; D006595:Hexosamines; C030791:valienamine; D007294:Inositol; C003749:validamycins; D000637:Transaminases
keywords: aminotransferase; biosynthesis; validamycin; valienone; β-valienamine