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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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