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


A spider-transmitted fungus (Rhizopus microspo-
rus) 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
benzolactones. We identified specific traits that serve as genetic
handles to find related salicylate macrolide pathways (lobata-
mide, oximidine, apicularen) in various other bacterial genera.
Knowledge of the biosynthetic pathway enables biosynthetic
engineering and genome-mining approaches.


DOI: 10.1002/anie.201916007

Projects: B1, Total ChemBioSys

Publication type: Not specified

Journal: Angew. Chem. Int. Ed.

Citation: S. P. Niehs, B. Dose, S. Richter, S. J. Pidot, H.-M. Dahse, T. P. Stinear, C. Hertweck, Angew. Chem. Int. Ed., 2020, 59, 7766-7771.

Date Published: 10th Feb 2020

Registered Mode: Not specified

Authors: Sarah Niehs, Benjamin Dose, Sophie Richter, Sacha J. Pidot, Timothy P. Stinear, Hans-Martin Dahse, Christian Hertweck

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Niehs, S. P., Dose, B., Richter, S., Pidot, S. J., Dahse, H. M., Stinear, T. P., & Hertweck, C. (2020). Mining Symbionts of a Spider‐Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones. Angewandte Chemie International Edition, 59(20), 7766–7771.

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Created: 23rd Sep 2020 at 14:48

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