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Fatty Acid Substitutions Modulate the Cytotoxicity of Puwainaphycins/Minutissamides Isolated from the Baltic Sea Cyanobacterium Nodularia harveyana UHCC-0300
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SYSNO ASEP 0558831 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Fatty Acid Substitutions Modulate the Cytotoxicity of Puwainaphycins/Minutissamides Isolated from the Baltic Sea Cyanobacterium Nodularia harveyana UHCC-0300 Author(s) Saurav, Kumar (MBU-M) ORCID
Caso, A. (IT)
Urajová, Petra (MBU-M)
Hrouzek, Pavel (MBU-M) ORCID
Esposito, G. (IT)
Delawská, Kateřina (MBU-M) ORCID
Macho, Markéta (MBU-M) ORCID
Hájek, Jan (MBU-M) ORCID
Cheel Horna, José (MBU-M)
Saha, Subhasish (MBU-M) ORCID
Divoká, Petra (MBU-M)
Arsin, S. (FI)
Sivonen, K. (FI)
Fewer, D. P. (FI)
Costantino, V. (IT)Source Title ACS Omega. - : American Chemical Society - ISSN 2470-1343
Roč. 7, č. 14 (2022), s. 11818-11828Number of pages 11 s. Language eng - English Country US - United States Keywords cyclic lipopeptides ; Puwainaphycins ; Minutissamides ; Cyanobacterium ; Nodularia harveyana ; UHCC-0300 OECD category Microbiology R&D Projects EF18_070/0010493 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GJ19-17868Y GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support MBU-M - RVO:61388971 UT WOS 000812945300001 EID SCOPUS 85127984540 DOI 10.1021/acsomega.1c07160 Annotation Puwainaphycins (PUW) and minutissamides (MIN) are structurally homologous cyclic lipopeptides that exhibit high structural variability and possess antifungal and cytotoxic activities. While only a minor variation can be found in the amino acid composition of the peptide cycle, the fatty acid (FA) moiety varies largely. The effect of FA functionalization on the bioactivity of PUW/MIN chemical variants is poorly understood. A rapid and selective liquid chromatography-mass spectrometry-based method led us to identify 13 PUW/MIN (1-13) chemical variants from the benthic cyanobacterium Nodularia harveyana strain UHCC-0300 from the Baltic Sea. Five new variants identified were designated as PUW H (1), PUW I (2), PUW J (4), PUW K (10), and PUW L (13) and varied slightly in the peptidic core composition, but a larger variation was observed in the oxo-, chloro-, and hydroxy-substitutions on the FA moiety. To address the effect of FA substitution on the cytotoxic effect, the major variants (3 and 5-11) together with four other PUW/MIN variants (14-17) previously isolated were included in the study. The data obtained showed that hydroxylation of the FA moiety abolishes the cytotoxicity or significantly reduces it when compared with the oxo-substituted C-18-FA (compounds 5-8). The oxo-substitution had only a minor effect on the cytotoxicity of the compound when compared to variants bearing no substitution. The activity of PUW/ MIN variants with chlorinated FA moieties varied depending on the position of the chlorine atom on the FA chain. This study also shows that variation in the amino acids distant from the FA moiety (position 4-8 of the peptide cycle) does not play an important role in determining the cytotoxicity of the compound. These findings confirmed that the lipophilicity of FA is essential to maintain the cytotoxicity of PUW/MIN lipopeptides. A 63 kb puwainaphycin biosynthetic gene cluster from a draft genome of the N. harveyana strain UHCC-0300 was identified. Ty. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2023 Electronic address https://pubs.acs.org/doi/10.1021/acsomega.1c07160
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