Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate‐Directed Formation of Quinolones versus Quinazolinones
| العنوان: | Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate‐Directed Formation of Quinolones versus Quinazolinones |
|---|---|
| المؤلفون: | Manuel Einsiedler, Cooper S. Jamieson, Mark A. Maskeri, Kendall N. Houk, Tobias A. M. Gulder |
| المصدر: | Angewandte Chemie (International Ed. in English) Angewandte Chemie (International ed. in English), vol 60, iss 15 |
| بيانات النشر: | John Wiley and Sons Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | FeII/α-ketoglutarate dependent dioxygenases, biocatalysis, Stereochemistry, natural products, Substituent, Quinolones, 010402 general chemistry, 01 natural sciences, Catalysis, Aspergillus nidulans, Dioxygenases, chemistry.chemical_compound, Biosynthesis, Dioxygenase, Reactivity (chemistry), enzyme mechanism, Research Articles, Quinazolinones, biology, Molecular Structure, 010405 organic chemistry, Organic Chemistry, Substrate (chemistry), General Medicine, General Chemistry, biology.organism_classification, 0104 chemical sciences, Biosynthesis | Hot Paper, chemistry, Biocatalysis, Chemical Sciences, Fe-II/alpha-ketoglutarate dependent dioxygenases, biosynthesis, Research Article |
| الوصف: | Previous studies showed that the FeII/α‐ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine‐2,5‐dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine‐2,5‐dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate‐directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance. AsqJ catalyzes a complex rearrangement sequence in quinolone biosynthesis. We show the AsqJ biocatalytic potential to significantly exceed this natural function. An unprecedented reaction pathway leading to quinazolinones is uncovered, functionally and mechanistically characterized in detail, revealing a unique substrate‐dependent product selectivity in enzyme catalysis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1521-3773 1433-7851 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5a17113512073a43015720906dfdaf3e http://europepmc.org/articles/PMC8049060 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5a17113512073a43015720906dfdaf3e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15213773 14337851 |
|---|