title: Enhanced production of acarbose and concurrently reduced formation of impurity c by addition of validamine in fermentation of Actinoplanes utahensis ZJB-08196.
abstract: Commercial production of acarbose is exclusively via done microbial fermentation with strains from the genera of Actinoplanes. The addition of C7N-aminocyclitols for enhanced production of acarbose and concurrently reduced formation of impurity C by cultivation of A. utahensis ZJB-08196 in 500-mL shake flasks was investigated, and validamine was found to be the most effective strategy. Under the optimal conditions of validamine addition, acarbose titer was increased from 3560 ± 128 mg/L to 4950 ± 156 mg/L, and impurity C concentration was concurrently decreased from 289 ± 24 mg/L to 107 ± 29 mg/L in batch fermentation after 168 h of cultivation. A further fed-batch experiment coupled with the addition of validamine (20 mg/L) in the fermentation medium prior to inoculation was designed to enhance the production of acarbose. When twice feedings of a mixture of 6 g/L glucose, 14 g/L maltose, and 9 g/L soybean flour were performed at 72 h and 96 h, acarbose titer reached 6606 ± 103 mg/L and impurity C concentration was only 212 ± 12 mg/L at 168 h of cultivation. Acarbose titer and proportion of acarbose/impurity C increased by 85.6% and 152.9% when compared with control experiments. This work demonstrates for the first time that validamine addition is a simple and effective strategy for increasing acarbose production and reducing impurity C formation.
authors.affiliation: Institute of Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Xue
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Qin
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Yuan-Shan
authors.initials: YS
authors.lastname: Wang
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Zheng
mesh_terms: D020909:Acarbose / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008848:Micromonosporaceae / Q000254:growth & development*
chemical_list: D003470:Culture Media; C042908:validamine; D007294:Inositol; D020909:Acarbose