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A full structure analysis of MDN-0066, a recently described cyclic lipodepsipeptide produced by Pseudomonas sp. bacteria

Vic De Roo (UGent) , Niels Geudens (UGent) , Yentl Verleysen (UGent) , Benjámin Kovács (UGent) , Feyisara Eyiwumi Oni (UGent) , Monica Höfte (UGent) , Annemieke Madder (UGent) and José Martins (UGent)
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Abstract
An increasing amount of bioactive non-ribosomal peptides find applications in modern medicine. One class in particular is the cyclic lipodepsipeptides (CLiPs), short oligopeptides, consisting of a mix of L- and D-amino acids which are cyclized via a lactone (depsi) bond between two amino acids and linked to a fatty acid moiety at the N-terminus. Research of these compounds has been fueled by their broad range of biological activities such as antimicrobial, cytotoxic, surfactant and recently described antineoplastic properties. In this poster, a full structural elucidation is presented for MDN-0066, a cyclic lipodepsipeptide, produced by Pseudomonas bacteria and of interest due to its antitumor activity. [1] MDN-0066 was successfully isolated from the bacterial strain Pseudomonas sp. SWRI-103 and found to be a member of the recently described CLiP family of the bananamides [2], implying the molecule consists of an octapeptide sequence, where six residues are incorporated in the macrocycle. The structure was investigated by liquid-state NMR spectroscopy and by means of nOe derived distance restraints, the conformation could be established. The stereochemistry of the individual amino acids was demonstrated by comparing the 1H-13C- HSQC spectra of both the natural product and chemically synthesized variants. The chemistry set in our synthetic efforts was guided by genomic prediction of the nonribosomal peptide synthetases (NRPSs), large multi-domain modules where each module has its own role in the biosynthesis. [3] Due to the combination of biological and chemical efforts a 3D-structure was able to be calculated, a first step towards unravelling the yet unknown modus operandi. References 1. Cautain, B., et al., Identification of the Lipodepsipeptide MDN-0066, a Novel Inhibitor of VHL/HIF Pathway Produced by a New Pseudomonas Species. PLOS ONE, 2015. 10(5): p. e0125221. 2. Nguyen, D.D., et al., Erratum: Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides. Nature Microbiology, 2017. 2: p. 17010. 3. Strieker, M., A. Tanović, and M.A. Marahiel, Nonribosomal peptide synthetases: structures and dynamics. Current Opinion in Structural Biology, 2010. 20(2): p. 234-240.

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Chicago
De Roo, Vic, Niels Geudens, Yentl Verleysen, Benjámin Kovács, Feyisara Eyiwumi Oni, Monica Höfte, Annemieke Madder, and José Martins. 2018. “A Full Structure Analysis of MDN-0066, a Recently Described Cyclic Lipodepsipeptide Produced by Pseudomonas Sp. Bacteria.” In Young Belgian Magnetic Resonance Scientist, 17th Symposium, Abstracts.
APA
De Roo, V., Geudens, N., Verleysen, Y., Kovács, B., Oni, F. E., Höfte, M., Madder, A., et al. (2018). A full structure analysis of MDN-0066, a recently described cyclic lipodepsipeptide produced by Pseudomonas sp. bacteria. Young Belgian Magnetic Resonance Scientist, 17th Symposium, Abstracts. Presented at the 17th Young Belgian Magnetic Resonance Scientist symposium  (YBMRS 2018).
Vancouver
1.
De Roo V, Geudens N, Verleysen Y, Kovács B, Oni FE, Höfte M, et al. A full structure analysis of MDN-0066, a recently described cyclic lipodepsipeptide produced by Pseudomonas sp. bacteria. Young Belgian Magnetic Resonance Scientist, 17th Symposium, Abstracts. 2018.
MLA
De Roo, Vic et al. “A Full Structure Analysis of MDN-0066, a Recently Described Cyclic Lipodepsipeptide Produced by Pseudomonas Sp. Bacteria.” Young Belgian Magnetic Resonance Scientist, 17th Symposium, Abstracts. 2018. Print.
@inproceedings{8585073,
  abstract     = {An increasing amount of bioactive non-ribosomal peptides find applications in modern medicine. One class in particular is the cyclic lipodepsipeptides (CLiPs), short oligopeptides, consisting of a mix of L- and D-amino acids which are cyclized via a lactone (depsi) bond between two amino acids and linked to a fatty acid moiety at the N-terminus. Research of these compounds has been fueled by their broad range of biological activities such as antimicrobial, cytotoxic, surfactant and recently described antineoplastic properties. In this poster, a full structural elucidation is presented for MDN-0066, a cyclic lipodepsipeptide, produced by Pseudomonas bacteria and of interest due to its antitumor activity. [1] MDN-0066 was successfully isolated from the bacterial strain Pseudomonas sp. SWRI-103 and found to be a member of the recently described CLiP family of the bananamides [2], implying the molecule consists of an octapeptide sequence, where six residues are incorporated in the macrocycle.
The structure was investigated by liquid-state NMR spectroscopy and by means of nOe derived distance restraints, the conformation could be established. The stereochemistry of the individual amino acids was demonstrated by comparing the 1H-13C- HSQC spectra of both the natural product and chemically synthesized variants. The chemistry set in our synthetic efforts was guided by genomic prediction of the nonribosomal peptide synthetases (NRPSs), large multi-domain modules where each module has its own role in the biosynthesis. [3] Due to the combination of biological and chemical efforts a 3D-structure was able to be calculated, a first step towards unravelling the yet unknown modus operandi.
References
1. Cautain, B., et al., Identification of the Lipodepsipeptide MDN-0066, a Novel Inhibitor of VHL/HIF Pathway Produced by a New Pseudomonas Species. PLOS ONE, 2015. 10(5): p. e0125221.
2. Nguyen, D.D., et al., Erratum: Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides. Nature Microbiology, 2017. 2: p. 17010.
3. Strieker, M., A. Tanovi\'{c}, and M.A. Marahiel, Nonribosomal peptide synthetases: structures and dynamics. Current Opinion in Structural Biology, 2010. 20(2): p. 234-240.},
  author       = {De Roo, Vic and Geudens, Niels and Verleysen, Yentl and Kov{\'a}cs, Benj{\'a}min and Oni, Feyisara Eyiwumi and H{\"o}fte, Monica and Madder, Annemieke and Martins, Jos{\'e}},
  booktitle    = {Young Belgian Magnetic Resonance Scientist, 17th Symposium, Abstracts},
  language     = {eng},
  location     = {Spa, Belgium},
  title        = {A full structure analysis of MDN-0066, a recently described cyclic lipodepsipeptide produced by Pseudomonas sp. bacteria},
  year         = {2018},
}