Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

Adwoa P Nartey; Aboagye K Dofuor; Kofi B A Owusu; Anil S Camas; Hai Deng; Marcel Jaspars; Kwaku Kyeremeh

doi:10.3762/bjoc.18.185

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

Beilstein J Org Chem. 2022 Dec 28:18:1763-1771. doi: 10.3762/bjoc.18.185. eCollection 2022.

Authors

Adwoa P Nartey^{1

2}, Aboagye K Dofuor³, Kofi B A Owusu⁴, Anil S Camas⁵, Hai Deng⁶, Marcel Jaspars⁶, Kwaku Kyeremeh¹

Affiliations

¹ Marine and Plant Research Laboratory of Ghana, Department of Chemistry, University of Ghana, P.O. Box LG 56 Legon-Accra, Ghana.
² Department of Biochemistry, Cell and Molecular Biology, University of Ghana, P.O. Box LG 54 Legon-Accra, Ghana.
³ Department of Biological, Physical and Mathematical Sciences, University of Environment and Sustainable Development, PMB, Somanya, Ghana.
⁴ Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon-Accra, Ghana.
⁵ Department of Biomedical Engineering, Faculty of Engineering, University of Samsun, Ballica Campus 55420, Samsun, Turkey.
⁶ Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Aberdeen AB24 3UE, Scotland, UK.

Abstract

During the continued isolation of different bacteria from highly diverse, low human activity environments in Ghana and the subsequent characterization and biological activity studies of their secondary metabolites, we found both Gram-positive and Gram-negative Bacillus strains to be ubiquitous and widespread. One of such strains, the Ghanaian novel Bacillus sp. strain DE2B was isolated from rhizosphere soils collected from the Digya National Park in Ghana. Chromatographic purifications of the fermented culture extract of the strain DE2B, led to the isolation of a cyclic lipopeptide, digyalipopeptide A (1). Using 1D and 2D NMR data, mass spectrometry sequence tagging, advanced Marfey's analysis, and the GNPS molecular networking we solved the full structure of digyalipopeptide A (1). We found that compound 1 is a member of a somewhat homologous series of peptides produced as a mixture by the strain containing the same amino acid sequence in the cyclic peptide backbone but differing only by the length of aliphatic fatty acid side chains. When tested against Trypanosoma brucei subsp. brucei strain GUTat 3.1 and Leishmania donovani (Laveran and Mesnil) Ross (D10), digyalipopeptide A (1) gave IC₅₀ values of 12.89 µM (suramin IC₅₀ 0.96 µM) and 4.85 µM (amphotericin B IC₅₀ 4.87 µM), respectively. Furthermore, digyalipopeptide A (1) produced IC₅₀ values of 10.07 µM (ampicillin IC₅₀ 0.18 µM) and 10.01 µM (ampicillin IC₅₀ 1.53 µM) for Staphylococcus aureus and Shigella sonnei, respectively. The selectivity and toxicity profile of compound 1 was investigated using normal cell lines, macrophages RAW 264.7. When tested against normal macrophages, compound 1 gave an IC₅₀ value of 71.32 μM. Selectivity indices (SI) were obtained by calculating the ratio of the IC₅₀ in RAW 264.7 to the IC₅₀ in the respective microbe and neglected parasite. In the presence of RAW 264.7 cell lines, compound 1 was particularly selective towards Leishmania donovani (Laveran and Mesnil) Ross (D10) with an SI value of 14.71. The bioactivity studies conducted confirm the role of these cyclic lipopeptides as defense chemicals in their natural environment and their ability to be biologically active across different species.

Keywords: Leishmania; lipopeptides; molecular networking; sequence tagging; trypanosomes.

Grants and funding

MR/S00520X/1/MRC_/Medical Research Council/United Kingdom