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The regulatory effect of citric acid on the co-production of poly(ε-lysine) and poly(l-diaminopropionic acid) in Streptomyces albulus PD-1

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Abstract

Streptomyces albulus PD-1 can co-produce antimicrobial homo-polymers poly(ε-lysine) (ε-PL) and poly(l-diaminopropionic acid) (PDAP). In this study, a novel feeding strategy of citric acid coupled with glucose-(NH4)2SO4 feeding was employed to S. albulus PD-1. When the pH of the culture broth dropped to 4.0, the feeding solution was added continuously to maintain the concentrations of glucose and citric acid at 10 and 4 g L−1, respectively. As a result, the final concentration of ε-PL increased from 21.7 to 29.7 g L−1 and the final concentration of PDAP decreased from 4.8 to 3.2 g L−1. Assays on intracellular nucleotide levels and key enzyme activities were performed to elucidate the underlying regulation mechanism. The addition of citric acid increased NADH/NAD+ ratio and decreased intracellular ATP level; meanwhile, the activities of pyruvate kinase, citrate synthase and isocitrate dehydrogenase decreased while aspartate aminotransferase activity increased. Therefore, we deduced that citric acid feeding resulted in metabolic flux redistribution at the node of phosphoenolpyruvate; the metabolic pathway from phosphoenolpyruvate directed into tricarboxylic acid cycle was weakened and thus PDAP production was inhibited. On the other hand, the metabolic pathway from phosphoenolpyruvate directed into oxaloacetate and l-aspartate was enhanced, thereby improving ε-PL production. This fermentation strategy may be potentially useful in ε-PL production because it can effectively inhibit the formation of by-products, such as PDAP.

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Acknowledgments

This work was supported by the National Nature Science Foundation of China (No. 21176123), the National Basic Research Program of China (973) (No. 2013CB733603), Specialized Research Fund for the Doctoral Program of Higher Education (No. 20113221130001) and Graduate Student Innovation Project of Jiangsu Province (No. CXZZ13_0464).

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Authors and Affiliations

  1. State Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing University of Technology, Nanjing, China

    Jun Xia, Zhaoxian Xu, Hong Xu, Xiaohai Feng & Fangfang Bo

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  1. Jun Xia
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  2. Zhaoxian Xu
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  3. Hong Xu
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  4. Xiaohai Feng
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  5. Fangfang Bo
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Correspondence to Hong Xu.

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J. Xia and Z. Xu had equal contributions to this work.

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Xia, J., Xu, Z., Xu, H. et al. The regulatory effect of citric acid on the co-production of poly(ε-lysine) and poly(l-diaminopropionic acid) in Streptomyces albulus PD-1. Bioprocess Biosyst Eng 37, 2095–2103 (2014). https://doi.org/10.1007/s00449-014-1187-4

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  • DOI: https://doi.org/10.1007/s00449-014-1187-4

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