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
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
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DOI：
10.1007/s12010-008-8502-y
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发表时间：
2009-01
影响因子：
3
通讯作者：
Xiangzhao Mao;Feng Wang;Jianguo Zhang;Shi Chen;Z. Deng;Yaling Shen;D. Wei
中科院分区：
文献类型：
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作者：
Xiangzhao Mao;Feng Wang;Jianguo Zhang;Shi Chen;Z. Deng;Yaling Shen;D. Wei
从链霉菌突变株的培养菌丝体中分离到一种新的低毒多烯大环内酯类抗生素FR-008/杀念菌素衍生物CS-103。FR-008，从其染色体上靶向缺失fscP细胞色素P450基因。为提高菌株CS103的生物合成能力，研究了菌株发酵过程中的pH变化和前体补料策略。FR-008在搅拌槽生物反应器中的开发。通过对工艺参数的分析，验证了该策略的有效性。CS103的最高浓度为139.98 μg/mL，是pH控制发酵的2.05倍。与非pH控制、pH控制和两阶段pH控制分批培养3种情况相比，所提出的“pH转移和前体补料策略”有效地避免了抗生素前体的稀缺，使CS103的生物量（YP/X）和底物（YP/S）产量分别提高了110.61%和48.52%，发酵时间由120 h缩短到96 h。最高的CS103生产率（1.46 μg mL−1h−1）的pH变化和前体补料策略是284.21%，97.30%，和58.70%，分别高于pH控制，pH控制，和两阶段pH控制的分批培养的情况下。
CS103, the novel derivative of polyene macrolides antibiotic FR-008/candicidin with lower toxicity has been isolated from the culture mycelia of the mutant ofStreptomycessp. FR-008, with targeted deletions of thefscPcytochrome P450 gene from its chromosome. To enhance biosynthesis of CS103, pH shift and precursor feeding strategy for fermentation process by the mutant ofStreptomycessp. 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 (YP/X) and substrate (YP/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−1h−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.