Nie Lishuang, Cao Mingming, Ji Qingqing, Gao Yuejiao, Wang Shaochen, Lyu Yunbin, Feng Zhiyang
College of Food Science and Technology, Nanjing Agricultural University, Weigang, Nanjing, 210095, China.
Curr Microbiol. 2022 Oct 6;79(11):336. doi: 10.1007/s00284-022-03039-5.
As bacterial natural products have been proved to be the most important source of many therapeutic medicines, the need to discover novel natural products becomes extremely urgent. Despite the fact that the majority of bacterial species are yet to be cultured in a laboratory setting, and that most of the bacterial natural product biosynthetic genes are silent, "metagenomics technology" offers a solution to help clone natural product biosynthetic genes from environmental samples, and genetic engineering enables the silent biosynthetic genes to be activated. In this work, a type II polyketide biosynthetic gene cluster was identified from a soil metagenomic library and was activated by over-expression of a SARP regulator gene in the gene cluster in Streptomyces hosts. A new tetracenomycin type compound tetracenomycin Y was identified from the fermentation broth. This study shows that metagenomics and genetic engineering could be combined to provide access to new natural metabolites.
由于细菌天然产物已被证明是许多治疗药物的最重要来源，发现新型天然产物的需求变得极为迫切。尽管大多数细菌物种尚未在实验室环境中培养，并且大多数细菌天然产物生物合成基因处于沉默状态，但“宏基因组学技术”提供了一种解决方案，有助于从环境样本中克隆天然产物生物合成基因，而基因工程能够激活沉默的生物合成基因。在这项工作中，从土壤宏基因组文库中鉴定出一个II型聚酮生物合成基因簇，并通过在链霉菌宿主中过表达该基因簇中的一个SARP调节基因来激活它。从发酵液中鉴定出一种新的四环素类化合物四环素Y。这项研究表明，宏基因组学和基因工程可以结合起来，以获取新的天然代谢产物。
