Abstract: Most of bacterial life remains functionally unexplored. This includes numerous deep-branching taxa that lack cultivated representatives and live in diverse habitats. Our lab uses metagenomic and single-cell-based mining strategies to investigate whether this massive taxonomic and ecological diversity is a resource of metabolic novelty. We have previously reported 'Entotheonella' symbionts of marine sponges as the first chemically "talented" producer taxon from microbial dark matter.^1,2  Most of their biosynthetic pathways have no counterparts in classical bacteria producer groups, such as actinomycetes, thus offering considerable pharmaceutical potential. The talk will present recent insights into the chemistry of sponge symbionts and other producers from uncultivated biomes. Using polytheonamides as an example,^3,4  opportunities and challenges will be addressed of accessing non-canonical natural products from uncultivated organisms that are only distantly related to available expression hosts.

[1] M. Wilson et al., Nature 2014, 506, 58.

[2] J.B. Cahn et al., Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 1718.

[3] M. F. Freeman et al., Science 2012, 338, 387.

[4] M. F. Freeman et al., Nat. Chem. 2017, 9, 387.