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, AndersAbstract
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; dehydroalaninePublished in
Molecules2019, 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