Enhanced Production of Acarbose and Concurrently Reduced Formation of Impurity C by Addition of Validamine in Fermentation of Actinoplanes utahensis ZJB-08196

• Main Authors: Ya-Ping Xue, Jun-Wei Qin, Ya-Jun Wang, Yuan-Shan Wang, Yu-Guo Zheng
• Format: Article
• Language: English
• Published: Hindawi Limited 2013-01-01
• Series: BioMed Research International
• Online Access: http://dx.doi.org/10.1155/2013/705418

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.