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Enhancing candicidin biosynthesis by medium optimization and pH stepwise control strategy with process metabolomics analysis of Streptomyces ZYJ-6

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Abstract

Candicidin is one of the most effective antimonilial agents. In order to enhance candicidin productivity, medium optimization and pH stepwise control strategy in process optimization were conducted by Streptomyces ZYJ-6. With the aid of Design Expert software and N/C/P-sources regulation, chemically defined medium fit for cell growth and candicidin biosynthesis was developed. Moreover, pH effects on cell growth and metabolism were investigated. The results indicated that the optimal pH for cell growth and candicidin biosynthesis were 6.8 and 7.8, respectively. The metabolomics analysis revealed that the pH stepwise control strategy (pH 6.8–7.8) combined the advantages of pH 6.8 and pH 7.8 and avoided precursor limitation in pH 6.8 and 7.8. Consequently, the pH stepwise control strategy played positive performance on cell growth and candicidin biosynthesis with the maximum titer of 5161 µg/mL. The titer of 5161 µg/mL was the highest level ever reported for candicidin production, which laid a solid foundation for industrial application. Additionally, pH stepwise control strategy was important reference for process optimization.

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Acknowledgements

We thank Prof. Dr. Delin You (Shanghai Jiao Tong University) for supplying Streptomyces ZYJ-6. This work was financially supported by a grant from the Major State Basic Research Development Program of China (973 Program, no. 2012CB721000G), NWO-MoST Joint Program (2013DFG32630) and national key special Program 2017YFF 0204600.

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, School of Biochemical Engineering, East China University of Science and Technology, Room 413, Building 18, Shanghai, 200237, People’s Republic of China

    Xiaoyun Liu, Xiaojuan Sun, Tong Wang, Xiwei Tian, Yingping Zhuang & Ju Chu

  2. Shanghai Guojia Bioengineering Technology Research Center Co., Ltd., Shanghai, 201403, People’s Republic of China

    Xin Zhang

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  1. Xiaoyun Liu
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  2. Xiaojuan Sun
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Correspondence to Ju Chu.

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Liu, X., Sun, X., Wang, T. et al. Enhancing candicidin biosynthesis by medium optimization and pH stepwise control strategy with process metabolomics analysis of Streptomyces ZYJ-6. Bioprocess Biosyst Eng 41, 1743–1755 (2018). https://doi.org/10.1007/s00449-018-1997-x

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  • DOI: https://doi.org/10.1007/s00449-018-1997-x

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