Heterologous Production of Lasso Peptide Capistruin in a Burkholderia Host
Heterologous Production of Lasso Peptide Capistruin in a Burkholderia Host
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DOI：
10.1021/acssynbio.9b00438
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发表时间：
2020-02-01
影响因子：
4.7
通讯作者：
Eustaquio, Alessandra S.
中科院分区：
文献类型：
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作者：
Kunakom, Sylvia;Eustaquio, Alessandra S.
伯克霍尔德氏菌是一种新兴的天然产物来源，在农业和医学中具有应用。生物合成基因簇的异源表达可以简化天然产物的发现;然而，通常使用的大肠杆菌宿主的产量通常较低。根据目前的模式，一个主机不适合所有，我们的目标是开发一个伯克霍尔德氏菌主机，最终利用伯克霍尔德氏菌基因组的生物合成潜力，其中每个基因组可以包含多达27个生物合成基因簇。由于密切的系统发育关系预计将提高成功的几率，由于兼容的基因表达和前体供应，我们测试了伯克霍尔德氏菌FERM BP-3421，一种非致病性分离株，以前用于生产天然产品在工业规模。我们在这里表明，FERM BP-3421可以产生模型套索肽capistruin的产量是至少65倍，高达580倍以上，比以前使用的E。coli宿主。
Burkholderia bacteria are an emerging source of natural products with applications in agriculture and medicine. The heterologous expression of biosynthetic gene clusters can streamline natural product discovery; however, production yields with the commonly used Escherichia coli host are usually low. Following the current paradigm that one host does not fit all, we aim to develop a Burkholderia host to ultimately tap into the biosynthetic potential of Burkholderia genomes, which can contain up to 27 biosynthetic gene clusters per genome. Because a close phylogenetic relationship is expected to improve the odds of success due to compatible gene expression and precursor supply, we tested Burkholderia sp. FERM BP-3421, a nonpathogenic isolate previously used to produce natural products at industrial scales. We show here that FERM BP-3421 can produce the model lasso peptide capistruin in yields that are at least 65 times and up to 580 times higher than the previously used E. coli host.