Johnston Chad W, Plumb Jonathan, Li Xiang, Grinstein Sergio, Magarvey Nathan A
The Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada L8N 3Z5.
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada L8N 3Z5.
Synth Syst Biotechnol. 2016 Feb 5;1(2):130-136. doi: 10.1016/j.synbio.2015.12.001. eCollection 2016 Jun.
Microbial natural products are a crucial source of bioactive molecules and unique chemical scaffolds. Despite their importance, rediscovery of known natural products from established productive microbes has led to declining interest, even while emergent genomic data suggest that the majority of microbial natural products remain to be discovered. Now, new sources of microbial natural products must be defined in order to provide chemical scaffolds for the next generation of small molecules for therapeutic, agricultural, and industrial purposes. In this work, we use specialized bioinformatic programs, genetic knockouts, and comparative metabolomics to define the genus as a new source of novel natural products. We show that spp. hold a diverse collection of biosynthetic gene clusters for the production of polyketide and nonribosomal peptide natural products. To confirm this bioinformatic survey, we create targeted mutants of and use comparative metabolomics to identify a novel polyketide surfactant. Using spectroscopic techniques, we show that this polyketide possesses a new chemical scaffold, and firmly demonstrate that this unexplored genus is a source for novel natural products.
微生物天然产物是生物活性分子和独特化学支架的重要来源。尽管它们很重要，但从已有的高产微生物中重新发现已知天然产物已导致人们的兴趣下降，即便新出现的基因组数据表明大多数微生物天然产物仍有待发现。现在，必须确定微生物天然产物的新来源，以便为用于治疗、农业和工业目的的下一代小分子提供化学支架。在这项工作中，我们使用专门的生物信息学程序、基因敲除和比较代谢组学来确定[具体属名]属作为新型天然产物的新来源。我们表明，[具体属名]菌属拥有用于生产聚酮化合物和非核糖体肽天然产物的多种生物合成基因簇。为了证实这一生物信息学调查结果，我们构建了[具体属名]菌属的靶向突变体，并使用比较代谢组学来鉴定一种新型聚酮表面活性剂。通过光谱技术，我们表明这种聚酮化合物具有一种新的化学支架，并有力地证明了这个未被探索的菌属是新型天然产物的一个来源。
