چکیده (انگلیسی):

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.