Work

Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate‐Directed Formation of Quinolones versus Quinazolinones

Year: 2021

Type: article

Abstract: 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.

Source: Angewandte Chemie

DOI: 10.1002/ange.202017086

Authors: Manuel Einsiedler, Cooper S. Jamieson, Mark A. Maskeri, Kendall N. Houk, Tobias A. M. Gulder

Institutions: Technische Universität Dresden, University of California, Los Angeles

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: hybrid

Estimated APC paid: $5,000

Funders: Deutsche Forschungsgemeinschaft, National Institute of General Medical Sciences