Mining Symbionts of a Spider‐Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones
Abstract: 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 benzolactones. We identified specific traits that serve as genetic handles to find related salicylate macrolide pathways (lobatamide, oximidine, apicularen) in various other bacterial genera. Knowledge of the biosynthetic pathway enables biosynthetic engineering and genome‐mining approaches.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Mining Symbionts of a Spider‐Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones ; volume:59 ; number:20 ; year:2020 ; pages:7766-7771 ; extent:6
Angewandte Chemie / International edition. International edition ; 59, Heft 20 (2020), 7766-7771 (gesamt 6)
- Creator
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Niehs, Sarah P.
Dose, Benjamin
Richter, Sophie
Pidot, Sacha J.
Dahse, Hans‐Martin
Stinear, Timothy P.
Hertweck, Christian
- DOI
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10.1002/anie.201916007
- URN
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urn:nbn:de:101:1-2022061212172407514673
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:35 AM CEST
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Associated
- Niehs, Sarah P.
- Dose, Benjamin
- Richter, Sophie
- Pidot, Sacha J.
- Dahse, Hans‐Martin
- Stinear, Timothy P.
- Hertweck, Christian
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Loss of Single‐Domain Function in a Modular Assembly Line Alters the Size and Shape of a Complex Polyketide
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