Heterologous Production of Lasso Peptide Capistruin in a Burkholderia Host.,ACS Synthetic Biology

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Heterologous Production of Lasso Peptide Capistruin in a Burkholderia Host.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-01-13 , DOI: 10.1021/acssynbio.9b00438
Sylvia Kunakom ₁ , Alessandra S Eustáquio ₁

Affiliation

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.

中文翻译：

伯克霍尔德杆菌宿主中套索肽 Capistruin 的异源生产。

伯克霍尔德氏菌是一种新兴的天然产物来源，在农业和医学领域有着广泛的应用。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，常用的大肠杆菌宿主的产量通常较低。遵循当前单一宿主不能适应所有宿主的范式，我们的目标是开发一种伯克霍尔德杆菌宿主，最终挖掘伯克霍尔德杆菌基因组的生物合成潜力，每个基因组最多可包含 27 个生物合成基因簇。由于兼容的基因表达和前体供应，密切的系统发育关系预计会提高成功的几率，因此我们测试了伯克霍尔德氏菌。FERM BP-3421，一种非致病性分离物，以前用于工业规模生产天然产品。我们在此表明，FERM BP-3421 可以产生模型套索肽 capistruin，其产量比之前使用的大肠杆菌宿主高至少 65 倍、最多 580 倍。

更新日期：2020-01-13

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