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*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
JournalOrganic Letters
Volume24
Issue number3
Pages (from-to)804-808
ISSN1523-7060
DOIs
Publication statusPublished - 28. Jan 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society

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