Enhancement of adenosine production by Bacillus subtilis CGMCC 4484 through metabolic flux analysis and simplified feedi
- PDF / 803,677 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 73 Downloads / 229 Views
ORIGINAL PAPER
Enhancement of adenosine production by Bacillus subtilis CGMCC 4484 through metabolic flux analysis and simplified feeding strategies Xiaochun Chen • Chunwei Zhang • Jian Cheng Xinchi Shi • Lei Li • Zhi Zhang • Jianxin Bai • Yong Chen • Shuya li • Hanjie Ying
•
Received: 10 December 2012 / Accepted: 14 April 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract The objective of this research was to understand how the initial glucose concentration influences adenosine (AR) production and metabolic flux shift on the cultivation of Bacillus subtilis CGMCC 4484. Experiments confirmed that initial glucose concentration affects cell growth, AR production and metabolites, significantly. The flux distribution at the key nodes of glucose-6-phosphate (G6P), pyruvate (PYR) and acetyl coenzyme-A (AcCoA) could be affected by changing the glucose concentration. Based on kinetic analysis of specific rates, the low-glucose concentration was better for both cell growth and AR production during the first 12 h. However, the high-glucose concentration was more favorable for AR formation after 18 h. Furthermore, different simplified feeding strategies were designed to achieve higher AR accumulation. The final AR concentration of 15.60 g L-1 was achieved when an optimized constant-feeding strategy was used, which was 21.02 % higher than batch fermentation. This was the first time to investigate the regulation of the glucose metabolism of AR-producing B. subtilis. Keywords Adenosine Bacillus subtilis Fed-batch Kinetic studies Metabolic flux analysis X. Chen and C. Zhang contributed equally to this study.
Electronic supplementary material The online version of this article (doi:10.1007/s00449-013-0959-6) contains supplementary material, which is available to authorized users. X. Chen C. Zhang J. Cheng X. Shi L. Li Z. Zhang J. Bai Y. Chen S. li H. Ying (&) State Key Laboratory of Materials-Oriented Chemical Engineering, College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009, People’s Republic of China e-mail: [email protected]
Introduction As an important endogenous purine nucleoside, adenosine (AR) has attracted considerable attention due to its significant medical applications in heart diseases, as it plays a pivotal role in coronary circulation and heart protection [1]. Previous experiments have shown that it is involved in numerous biochemical and physiological processes including tissue protection and repair, neurotransmission and anti-inflammatory activity [2, 3]. Furthermore, AR is important as a precursor of nucleotides that have flavoring properties and as a pharmaceutical intermediate in the synthesis of adenosine triphosphate (ATP) [4, 5]. Industrial production of AR can be achieved by chemical or biological synthesis. Currently, driven by economic and environmental considerations, industrial production of AR via biological routes has been intensified. In comparison with the chemical synthesis, microbial production of AR has su
Data Loading...
