Jan 17, 2009

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

Applied Biochemistry and Biotechnology
Xiangzhao MaoDongzhi Wei

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 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% high...Continue Reading

Mentioned in this Paper

Macrolide Antibiotics
Cytochrome P450
Polyenes
Macrolides
Vanobid
Cytochrome P450 Activity
Chromosomes
Mutant
Fermentation
Candicidin

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