P134: MS-guided genome mining of marine actinomycetes

As more and more genomes are sequenced, there is a need for time- and work-effective genome mining methods for the discovery of unprecedented, bioactive natural products. Experiment-guided genome mining allows a higher throughput rate than other genome mining methods as multiple expressed pathways can be screened in one experiment. In our lab, genome mining methods such as peptidogenomics and a new glycogenomic concept were developed. Peptidic and glycosylated natural products can be easily identified by specific MSn structures such as amino acid sequence tags or sugar fragments, respectively, that allow the direct connection to genome-encoded biosynthetic enzymes or precursor peptides. The new glycogenomic concept is based on the generation and dereplication of tandem MS fragments of aglyca and their attached sugars. The compound of interest can be connected to its biosynthetic gene cluster by the presence of specific genes responsible for the biosynthesis of desoxysugars and their attachment to the aglycon. Marine bacteria present a prolific source of bioactive and structurally diverse compounds. Parts of the vast collection of genome-sequenced Salinispora and Streptomyces strains at Scripps Institution of Oceanography were cultured in solid and liquid media, extracted with different solvents and then screened for new peptidic and glycosylated compounds. Recent progress on the isolation, characterization and biosynthetic analysis of new natural products from these marine actinomycetes is presented to highlight the MS-guided genome mining workflow.