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Research article - Peer-reviewed, 2019

Antibacterial Isoquinoline Alkaloids from the Fungus Penicillium Spathulatum Em19

Nord, Christina; Levenfors, Jolanta; Bjerketorp, Joakim; Sahlberg, Christer; Guss, Bengt; Öberg, Bo; Broberg, Anders

Abstract

In the search for new microbial antibacterial secondary metabolites, two new compounds (1 and 2) were isolated from culture broths of Penicillium spathulatum Em19. Structure determination by nuclear magnetic resonance and mass spectrometry identified the compounds as 6,7-dihydroxy-5,10-dihydropyrrolo[1,2-b]isoquinoline-3-carboxylic acid (1, spathullin A) and 5,10-dihydropyrrolo[1,2-b]isoquinoline-6,7-diol (2, spathullin B). The two compounds displayed activity against both Gram-negative and -positive bacteria, including Escherichia coli, Acinetobacterbaumannii, Enterobactercloacae, Klebsiellapneumonia, Pseudomonasaeruginosa, and Staphylococcusaureus. Compound 2 was more potent than 1 against all tested pathogens, with minimal inhibitory concentrations down to 1 mu g/mL (5 mu M) against S. aureus, but 2 was also more cytotoxic than 1 (50% inhibitory concentrations 112 and 11 mu M for compounds 1 and 2, respectively, towards Huh7 cells). Based on stable isotope labelling experiments and a literature comparison, the biosynthesis of 1 was suggested to proceed from cysteine, tyrosine and methionine via a non-ribosomal peptides synthase like enzyme complex, whereas compound 2 was formed spontaneously from 1 by decarboxylation. Compound 1 was also easily oxidized to the 1,2-benzoquinone 3. Due to the instability of compound 1 and the toxicity of 2, the compounds are of low interest as possible future antibacterial drugs.

Keywords

antibiotic resistance; antibacterial secondary metabolites; secondary metabolism; Penicillium; isoquinoline alkaloids; dehydroalanine

Published in

Molecules
2019, volume: 24, number: 24, article number: 4616

Authors' information

Nord, Christina
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Ultupharma
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Ultupharma
Sahlberg, Christer
Medivir AB
Swedish University of Agricultural Sciences, Department of Biomedical Science and Veterinary Public Health
Öberg, Bo
Ultupharma
Swedish University of Agricultural Sciences, Department of Molecular Sciences

Sustainable Development Goals

SDG3 Good health and wellbeing

UKÄ Subject classification

Microbiology

Publication Identifiers

DOI: https://doi.org/10.3390/molecules24244616

URI (permanent link to this page)

https://res.slu.se/id/publ/103675