P171: Informatic Mining of Microbiomes for Bioactive Natural Products

A vast number of currently used human therapeutics are microbially derived secondary metabolites from ecologically diverse organisms. While many organisms have been extensively mined for bioactive compounds, a vast cross-section of microbial diversity has not and this includes organisms which reside in, or on, the human body, the human microbiome. Common themes have emerged from prior research into bioactive microbial secondary metabolites relating to the machinery used in secondary metabolite synthesis. Prominent among these strategies are the assembly-line like enzymes, the polyketide synthases and nonribosomal peptide synthetases that create the polyketides (e.g. erythromycin, rapamycin) and nonribosomal peptides (e.g. penicillin, cyclosporine), respectively. The well appreciated strategies of how microbes create bioactive small molecules and rapid genomic sequencing is opening new ways to find bioactive secondary metabolites independent of classical bioactive guided isolation.

In this research talk a focal point will be placed on the enabling technologies and strategies used to explore the suite of genetically-encoded small molecule natural products produced by members of the human microbiotia and underexplored environmental microbiomes. One of strategies that will be discussed is an informatic search algorithm for natural products (iSNAP) algorithm that we have developed as a database-driven dereplication/discovery tool to mine genomes for novel small molecule structures independent of bioactivity guided isolation. Examples of the application of the iSNAP strategy as it applies to nonribosomal peptides and ribosomal peptides will be provided and the novel scaffolds and actions of these molecules presented.