Journal article

Mining Symbionts of a Spider‐Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones

Sarah P Niehs, Benjamin Dose, Sophie Richter, Sacha J Pidot, Hans‐Martin Dahse, Timothy P Stinear, Christian Hertweck

Angewandte Chemie | Wiley | Published : 2020


A spider-transmitted fungus (Rhizopus microsporus) that was isolated from necrotic human tissue was found to harbor endofungal bacteria (Burkholderia sp.). Metabolic profiling of the symbionts revealed a complex of cytotoxic agents (necroximes). Their structures were characterized as oxime-substituted benzolactone enamides with a peptidic side chain. The potently cytotoxic necroximes are also formed in symbiosis with the fungal host and could have contributed to the necrosis. Genome sequencing and computational analyses revealed a novel modular PKS/NRPS assembly line equipped with several non-canonical domains. Based on gene-deletion mutants, we propose a biosynthetic model for bacterial ben..

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