Journal article
Biosynthesis of Calipyridone A Represents a Fungal 2-Pyridone Formation without Ring Expansion in Aspergillus californicus
Department of Biotechnology and Biomedicine, Technical University of Denmark1
Eukaryotic Molecular Cell Biology, Section for Synthetic Biology, Department of Biotechnology and Biomedicine, Technical University of Denmark2
Natural Product Discovery, Section for Microbial and Chemical Ecology, Department of Biotechnology and Biomedicine, Technical University of Denmark3
University of Brescia4
University of Southern Denmark5
Center for Microbial Secondary Metabolites, Centers, Technical University of Denmark6
A chemical investigation of the filamentous fungus Aspergillus californicus led to the isolation of a polyketide-nonribosomal peptide hybrid, calipyridone A ( 1 ). A putative biosynthetic gene cluster cpd for production of 1 was next identified by genome mining. The role of the cpd cluster in the production of 1 was confirmed by multiple gene deletion experiments in the host strain as well as by heterologous expression of the hybrid gene cpdA in Aspergillus oryzae.
Moreover, chemical analyses of the mutant strains allowed the biosynthesis of 1 to be elucidated. The results indicate that the generation of the 2-pyridone moiety of 1 via nucleophilic attack of the iminol nitrogen to the carbonyl carbon is different from the biosynthesis of other fungal 2-pyridone products through P450-catalyzed tetramic acid ring expansions.
In addition, two biogenetic intermediates, calipyridones B and C, showed modest inhibition effects on the plaque-forming ability of SARS-CoV-2.
| Language: | English |
|---|---|
| Publisher: | American Chemical Society |
| Year: | 2022 |
| Pages: | 804-808 |
| ISSN: | 15237052 and 15237060 |
| Types: | Journal article |
| DOI: | 10.1021/acs.orglett.1c03792 |
| ORCIDs: | Guo, Yaojie , 0000-0001-5468-7715 , Mortensen, Uffe H. , Larsen, Thomas O. , Contesini, Fabiano J. and Wang, Xinhui |
