A chromatogram-simplified Streptomyces albus host for heterologous production of natural products

A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
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用于异源生产天然产物的色谱简化白色链霉菌宿主

DOI:
10.1101/612291
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发表时间:
2019
期刊:
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影响因子:
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通讯作者:
Fazal A
Fazal A
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作者:
Fazal A

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从培养或未培养的来源中克隆天然产物生物合成基因簇并随后通过遗传上易处理的异源宿主表达是阐明和表征新型微生物天然产物的重要策略。合适的表达宿主的可用性是此工作流程的关键方面。在这项工作中,我们从白色链霉菌S4中诱变了5个内源生物合成基因簇,从而降低了菌株产生的化学提取物的复杂性,并消除了抗真菌和抗细菌活性。我们发现,所产生的五元突变体可以表达外源生物合成基因簇异源生产放线菌紫素,肉桂霉素和prunustatin。我们设想,我们的菌株将是一个有用的除了不断增长的套件异源表达主机可用于探索微生物次生代谢。
Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters fromStreptomyces albusS4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism.
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