Biosynthesis of Calipyridone A Represents a Fungal 2-Pyridone Formation without Ring Expansion in Aspergillus californicus

Yaojie Guo, Fabiano J. Contesini, Xinhui Wang, Simone Ghidinelli, Ditte S. Tornby, Thomas E. Andersen, Uffe H. Mortensen, Thomas O. Larsen*

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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 inAspergillus 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.

OriginalsprogEngelsk
TidsskriftOrganic Letters
Vol/bind24
Udgave nummer3
Sider (fra-til)804-808
ISSN1523-7060
DOI
StatusUdgivet - 28. jan. 2022

Bibliografisk note

Funding Information:
The authors thank Dr. Kasper Enemark-Rasmussen from the Department of Chemistry, Technical University of Denmark (DTU) for acquiring NMR data and Master’s student Emil H. Kristiansen from DTU Bioengineering for the chemical extraction. Mercedes de la Cruz, Thomas A. Mackenzie, Carmen R. Martín, and Pilar Sánchez from Fundación MEDINA in Spain are acknowledged for the antibacterial and cytotoxic tests. Professor Soizic Prado from Muséum National d’Histoire Naturelle, Unité Molécules de Communication et Adaptation des Micro-Organismes (UMR 7245), CNRS, Sorbonne Université, France, is acknowledged for her suggestions on the manuscript. Computations were enabled by the HPC Infrastructure of the DTU Computing Center. Y.G. is the recipient of a scholarship (201709110107) from the China Scholarship Council. The authors thank the Novo Nordisk Foundation (NNF15OC0016610) and Innovation Fund Denmark (6150-00031B.9) for their grant support.

Funding Information:
The authors thank Dr. Kasper Enemark-Rasmussen from the Department of Chemistry, Technical University of Denmark (DTU) for acquiring NMR data and Master?s student Emil H. Kristiansen from DTU Bioengineering for the chemical extraction. Mercedes de la Cruz, Thomas A. Mackenzie, Carmen R. Marti?n, and Pilar Sa?nchez from Fundacio?n MEDINA in Spain are acknowledged for the antibacterial and cytotoxic tests. Professor Soizic Prado from Muse?um National d?Histoire Naturelle, Unite? Mole?cules de Communication et Adaptation des Micro-Organismes (UMR 7245), CNRS, Sorbonne Universite?, France, is acknowledged for her suggestions on the manuscript. Computations were enabled by the HPC Infrastructure of the DTU Computing Center. Y.G. is the recipient of a scholarship (201709110107) from the China Scholarship Council. The authors thank the Novo Nordisk Foundation (NNF15OC0016610) and Innovation Fund Denmark (6150-00031B.9) for their grant support.

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