The pH shift and precursor feeding strategy in a low-toxicity FR-008/candicidin derivative CS103 fermentation bioprocess by a mutant of Streptomyces sp. FR-008.
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 microg/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 microg 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.
Mao
Xiangzhao
X
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, People's Republic of China.
Wang
Feng
F
Zhang
Jianguo
J
Chen
Shi
S
Deng
Zixin
Z
Shen
Yaling
Y
Wei
Dongzhi
D
D002174:Candicidin / Q000737:chemistry / Q000378:metabolism*; D005285:Fermentation / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D002174:Candicidin