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BioMed Research International
Volume 2013 (2013), Article ID 705418, 9 pages
Research Article

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

1Institute of Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
2Engineering Research Center of Bioconversion and Biopurification of Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
3Huadong Medicine Co., Ltd., Hangzhou, Zhejiang 310011, China

Received 4 September 2012; Revised 28 November 2012; Accepted 2 December 2012

Academic Editor: Jozef Anné

Copyright © 2013 Ya-Ping Xue et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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  mg/L to  mg/L, and impurity C concentration was concurrently decreased from  mg/L to  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  mg/L and impurity C concentration was only  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.