多黏菌素B发酵过程中组分与杂质的调节
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摘要
多黏菌素B是一种由多黏类芽孢杆菌(Paenibacillus polymyxa)产生的氨基酸和脂肪组成的碱性多肽类抗生素。以产多黏菌素B的多黏芽孢杆菌Paenibacillus polymyxa ATCC10401为出发菌株,考察了不同量和不同组合方式的前体氨基酸添加对各个组分的影响。通过试验和HPLC分析,得到了高质量分数多黏菌素B1的发酵生产方法,多黏菌素B1的质量分数达到80%以上。
Polymyxin B(PMB) is a kind of alkaline cyclic polypeptide antibiotics composed of amino acids and fatty acid. In this paper, the effects of different amounts and different combinations of amino acid precursors on PMB components was studied with Paenibacillus polymyxa ATCC10401 as producing strain. A fermentation method with high titer of Polymyxin B1 was established, and the content of Polymyxin B1 is higher than 80%.
Polymyxin B(PMB) is a kind of alkaline cyclic polypeptide antibiotics composed of amino acids and fatty acid. In this paper, the effects of different amounts and different combinations of amino acid precursors on PMB components was studied with Paenibacillus polymyxa ATCC10401 as producing strain. A fermentation method with high titer of Polymyxin B1 was established, and the content of Polymyxin B1 is higher than 80%.
引文
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[8] 方声,赖月琴,陈斌,等.流加补料技术在大观霉素发酵中的应用[J].发酵科技通讯,2018,47(2):92-96.
[9] 方声,余斌,章鹏鹏.卡那霉素连续补料发酵工艺的研究[J].发酵科技通讯,2018,47(1):48-51.
[10] 王炫,谢希贤,蔡传康,等.谷氨酸棒杆菌KGA-3产а -酮戊二酸补料分批发酵工艺优化[J].发酵科技通讯,2016,45(1):45-49.
[11] 郭成林,孙东昌,裘娟萍,等.抗耐药菌药物多粘菌素生物合成及其应用研究进展[J].科技通报,2016,32(3):58-62.
[2] AHMED M U, VELKOV T, LIN Y W, et al. Potential toxicity of polymyxins in human lung epithelial cells[J]. Antimicrobial agents and chemotherapy, 2017,61(6):1-12.
[3] KWA A, KASIAKOU S K, TAM V H, et al. Polymyxin B: similarities to and differences from colistin (polymyxin E)[J]. Expert review of anti-infective therapy, 2007,5(5):811-821.
[4] HE J, GAO S, HU M, et al. A validated ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of polymyxin B in mouse serum and epithelial lining fluid: application to pharmacokinetic studies[J]. Journal of antimicrobial chemotherapy, 2016,68(5):1104-1110.
[5] CUI A L, HU X X, GAO Y, et al. Synthesis and bioactivity investigation of the individual components of cyclic lipopeptide antibiotics[J]. Journal of medicinal chemistry, 2018,61(5):1845-1857.
[6] SIVANESAN S, ROBERTS K, WANG J P, et al. Pharmacokinetics of the individual major components of polymyxin B and colistin in rats[J]. Journal of natural products, 2017,80(1):225-229.
[7] ROBERTS K D, AZAD M A K, WANG J P, et al. Antimicrobial activity and toxicity of the major lipopeptide components of polymyxin B and colistin:Last-line antibiotics against multidrug-resistant gram-negative bacteria[J]. Acs infectious diseases, 2015,1(11):568-575.
[8] 方声,赖月琴,陈斌,等.流加补料技术在大观霉素发酵中的应用[J].发酵科技通讯,2018,47(2):92-96.
[9] 方声,余斌,章鹏鹏.卡那霉素连续补料发酵工艺的研究[J].发酵科技通讯,2018,47(1):48-51.
[10] 王炫,谢希贤,蔡传康,等.谷氨酸棒杆菌KGA-3产а -酮戊二酸补料分批发酵工艺优化[J].发酵科技通讯,2016,45(1):45-49.
[11] 郭成林,孙东昌,裘娟萍,等.抗耐药菌药物多粘菌素生物合成及其应用研究进展[J].科技通报,2016,32(3):58-62.