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 decli...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 Legionella as a new source of novel natural products.We show that Legionella 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 L.pneumophila 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.展开更多
基金generous gifts from McMaster University and the Canadian Institute of Health Research(CIHR).C.Johnston is funded through a CIHR Doctoral Research Award.N.Magarvey is funded by a CIHR New Investigator Award.We wish to thank Dr.Cyril Guyard for providing L.pneumophila LP02,as well as the GFP-expression plasmid pBH6119.
文摘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 Legionella as a new source of novel natural products.We show that Legionella 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 L.pneumophila 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.
