Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Genome mining and chemical characterization of a new cyclic lipopeptide associated with MDN-0066 from Pseudomonas moraviensis HN2 cultured in a valine-rich medium

The Journal of Antibiotics volume 76, pages 244–248 (2023)Cite this article

Subjects

Abstract

A new cyclic lipopeptide (CLP) MDN-0066-β (1) and MDN-0066 (2) were isolated and characterized from the bacterial cultures of P. moraviensis HN2 in this study. The CLPs were purified by solid-phase extraction (SPE) and reversed-phase high performance liquid chromatography (RP-HPLC). Moreover, chemical structures of two CLPs were characterized by genome mining and analysis, nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), Marfey’s method and (C-H)α NMR fingerprint matching approach. MDN-0066 (2) has an amino acid sequence of l-Leu1, d-Glu2, d-allo-Thr3, d-Leu4, d-Leu5, d-Ser6, l-Leu7, l-Ile8 linked to a saturated C10 β-hydroxyl fatty acid moiety (R-configuration for 3-OH). The new CLP MDN-0066-β (1) differs MDN-0066 (2) in the 8th position of l-valine in its peptide moiety, this variation in structure could be attributed to the supplement of l-valine in the cultural medium during liquid fermentation. Further antimicrobial tests showed that the two CLPs display moderate antagonistic activity against Staphylococcus aureus and Escherichia coli.

Pseudomonas species are Gram negative bacteria consisting of more than 310 type strains [1]. CLPs, composed of an amino sequence and a fatty acid tail, are valuable molecules synthesized by nonribosomal peptide synthetases (NRPSs). The biosynthetic gene clusters (BGCs) in the genome of Pseudomonas spp. encoding of NRPSs are normally orphan gene clusters [2]. CLPs are capable of interacting with versatile cellular membranes and thus they display a broad spectrum of bioactivities, such as antifungal, antibacterial, antiviral properties, and the inhibitory effect on human cancer cells [3, 4]. Thus, developing of new natural-derived CLPs from Pseudomonas sp. are an important way to explore drug candidates. Instead of traditional methods, genome mining and analysis of the BGC responsible for synthesizing NRPS of the CLPs is intensively used for the discovery of CLPs recently [5].

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Girard L, Lood C, Höfte M, Vandamme P, Rokni-Zadeh H, van Noort V, et al. The ever-expanding Pseudomonas genus: description of 43 new species and partition of the Pseudomonas putida group. Microorganisms. 2021;9:1766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gross H, Loper JE. Genomics of secondary metabolite production by Pseudomonas spp. Nat Prod Rep. 2009;26:1408–46.

    Article  CAS  PubMed  Google Scholar 

  3. Götze S, Stallforth P. Structure, properties, and biological functions of nonribosomal lipopeptides from pseudomonads. Nat Prod Rep. 2020;37:29–54.

    Article  PubMed  Google Scholar 

  4. Geudens N, Martins JC. Cyclic lipodepsipeptides from Pseudomonas spp.—biological Swiss-army knives. Front Microbiol. 2018;9:1867.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Albarano L, Esposito R, Ruocco N, Costantini M. Genome mining as new challenge in natural products discovery. Mar Drugs. 2020;18:199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ma Z, Hu J. Complete genome sequence of a marine-sediment-derived bacterial strain Bacillus velezensis SH-B74, a cyclic lipopeptides producer and a biopesticide. 3 Biotech. 2019;9:162.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Meier-Kolthoff JP, Göker M. TYGS is an automated high-throughput platform for state-of-the-art genome-based taxonomy. Nat Commun. 2019;10:2182.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Blin K, Shaw S, Kloosterman AM, Charlop-Powers Z, van Wezel GP, Medema Marnix H, et al. antiSMASH 6.0: improving cluster detection and comparison capabilities. Nucleic Acids Res. 2021;49:W29–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nguyen DD, Melnik A, Koyama N, Lu X, Schorn M, Fang J, et al. Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides. Nat Microbiol. 2017;2:16197.

    Article  Google Scholar 

  10. Omoboye OO, Geudens N, Duban M, Chevalier M, Flahaut C, Martins JC, et al. Pseudomonas sp. COW3 produces new bananamide-type cyclic lipopeptides with antimicrobial activity against Pythium myriotylum and Pyricularia oryzae. Molecules 2019;24:4170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zarvandi S, Bahrami T, Pauwels B, Asgharzadeh A, Hosseini-Mazinani M, Salari F, et al. Draft genome sequence of cyclic lipopeptide producer Pseudomonas sp. strain SWRI103, isolated from wheat rhizosphere. Microbiol Resour Announc. 2020;9:e00538–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Girard L, Geudens N, Pauwels B, Höfte M, Martins JC, De Mot R. Transporter gene-mediated typing for detection and genome mining of lipopeptide-producing Pseudomonas. Applied. Environ Microbiol. 2021;88:e0186921.

    Article  Google Scholar 

  13. Sambrooke J, Fritsch EF, Maniatis T, editors. Molecular Cloning: A Laboratory Manual. 2nd ed. Cold Spring Harbor: Cold Spring Harbor Laboratory Press;1989.

  14. King EO, Ward MK, Raney DE. Two simple media for the demonstration of pyocyanin and fluorescin. J Lab Clin Med. 1954;44:301–7.

    CAS  PubMed  Google Scholar 

  15. Vijayasarathy S, Prasad P, Fremlin LJ, Ratnayake R, Salim AA, Khalil Z, et al. C3 and 2D C3 Marfey’s methods for amino acid analysis in natural products. J Nat Prod. 2016;79:421–7.

    Article  CAS  PubMed  Google Scholar 

  16. De Roo V, Verleysen Y, Kovács B, De Vleeschouwer M, Muangkaew P, Girard L, et al. An nuclear magnetic resonance fingerprint matching approach for the identification and structural re-evaluation of Pseudomonas Lipopeptides. Microbiol Spectr. 2022;10:e0126122.

    Article  PubMed  Google Scholar 

  17. Cautain B, de Pedro N, Schulz C, Pascual J, da S, Sousa T, Martin J, 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:e0125221.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ma Z, Wang N, Hu J, Wang S. Isolation and characterization of a new iturinic lipopeptide, mojavensin A produced by a marine-derived bacterium Bacillus mojavensis B0621A. J Antibiot (Tokyo). 2012;65:317–22.

    Article  CAS  PubMed  Google Scholar 

  19. Ma Z, Zhang S, Zhang S, Wu G, Shao Y, Mi Q, et al. Isolation and characterization of a new cyclic lipopeptide surfactin from a marine-derived Bacillus velezensis SH-B74. J Antibiot (Tokyo). 2020;73:863–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The research of Z. Ma’s lab was supported by the grants from the National Natural Science Foundation of China (no. 32060625) and the Natural Science Foundation of Gansu Province (no. 20JR5RA527).

Author information

Authors and Affiliations

  1. College of Life Science, Northwest Normal University, 967 East Anning Road, 730070, Lanzhou, China

    Zongwang Ma

Authors
  1. Zongwang Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZM conceived and designed the study, conducted all the experiments and wrote the manuscript.

Corresponding author

Correspondence to Zongwang Ma.

Ethics declarations

Conflict of interest

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, Z. Genome mining and chemical characterization of a new cyclic lipopeptide associated with MDN-0066 from Pseudomonas moraviensis HN2 cultured in a valine-rich medium. J Antibiot 76, 244–248 (2023). https://doi.org/10.1038/s41429-023-00597-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-023-00597-z

This article is cited by

Search

Advanced search

Quick links