The pH Shift and Precursor Feeding Strategy in a Low-Toxicity FR-008/Candicidin Derivative CS103 Fermentation Bioprocess by a Mutant of <Emphasis Type="Italic">Streptomyces</Emphasis> sp. FR-008 |
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Authors: | Xiangzhao Mao Feng Wang Jianguo Zhang Shi Chen Zixin Deng Yaling Shen Dongzhi Wei |
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Institution: | (1) State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China;(2) Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266071, People’s Republic of China;(3) Laboratory of Microbial Metabolism and School of Life Science & Biotechnology, Shanghai Jiaotong University, Shanghai, 200030, People’s Republic of China; |
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Abstract: | CS103, the novel derivative of polyene macrolides antibiotic FR-008/candicidin with lower toxicity has been isolated from
the culture mycelia of the mutant of Streptomyces sp. FR-008, with targeted deletions of the fscP cytochrome P450 gene from its chromosome. To enhance biosynthesis of CS103, pH shift and precursor feeding strategy for fermentation
process by the mutant of Streptomyces sp. FR-008 in a stirred tank bioreactor was developed. According to the process parameters analysis, the effectiveness of
the strategy was examined and confirmed by experiments. A maximal CS103 concentration of 139.98 μg/mL was obtained, 2.05-fold
higher than that in the pH-uncontrolled fermentation. Compared to other three cases as pH-uncontrolled, pH-controlled, and
two-stage pH-controlled batch cultures, the proposed “pH shift and precursor feeding strategy” effectively avoided the scarcity
of the antibiotic precursor, increased the CS103 yield from biomass (Y
P/X) and substrate (Y
P/S) by 110.61% and 48.52%, respectively, and at the time the fermentation time was shortened from 120 to 96 h. The highest CS103
production rate (1.46 μg mL−1 h−1) of the pH shift and precursor feeding strategy was 284.21%, 97.30%, and 58.70% higher than that of pH-uncontrolled, pH-controlled,
and two-stage pH-controlled batch culture cases, respectively. |
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