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Isolation and synthesis of a new cyclic tetrapeptide from marine-associated Bacillus sp. and its bacterial biofilm formation inhibitory activity

The Journal of Antibiotics volume 78, pages 408–417 (2025)Cite this article

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Abstract

A new cyclic tetrapeptide named Cereusitin B (1), along with a number of known cyclic dipeptides was isolated from the fermentation broth of a marine-associated Bacillus sp. I-2. The structure of Cereusitin B, cyclo-(l-phenylalanyl-trans-4-hydroxy-l-prolyl-l-leucyl-l-alanine), was determined through extensive analysis using high-resolution electrospray ionization mass spectrometry and NMR spectral data (1D, 2D NMR), and its identity was further confirmed by Marfey’ method and chemical synthesis. The antimicrobial activity tests showed that compound 2 was moderately active against Candida albicans with a MIC value of 125 µg mL−1, while the other compounds exhibited no antimicrobial activity at the experimental concentrations. In addition, compound 1 showed the ability to inhibit the formation of S. aureus biofilm.

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References

  1. Bowler P, Murphy C, Wolcott R. Biofilm exacerbates antibiotic resistance: is this a current oversight in antimicrobial stewardship?. Antimicrob Resist Infect Control. 2020;9:162.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rossiter SE, Fletcher MH, Wuest WM. Natural products as platforms to overcome antibiotic resistance. Chem Rev. 2017;117:12415–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yin QJ, Ying TT, Zhou ZY, Hu GA, Yang CL, Hua Y, et al. Species-specificity of the secondary biosynthetic potential in Bacillus. Front Microbiol. 2023;14:1271418.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Iqbal S, Begum F, Rabaan AA, Aljeldah M, Shammari BRA, Alawfi A, et al. Classification and multifaceted potential of secondary metabolites produced by group: a comprehensive review. Molecules. 2023;28:927.

  5. Pinzón-Espinosa A, Martinez-Matamoros D, Castellanos L, Duque C, Rodríguez J, Jiménez C, et al. Cereusitin A, a cyclic tetrapeptide from a Bacillus cereus strain isolated from the soft coral Antillogorgia (syn. Pseudopterogorgia) elisabethae. Tetrahedron Lett. 2017;58:634–7.

    Article  Google Scholar 

  6. Kaur H, Heapy AM, Brimble MA. Synthesis of the antifungal cyclic peptides Tunicyclins C and D. Synlett. 2012;2:275–7.

  7. Zhao C, Qu JJ, Peng F, Lu RL, Bao GH, Huang B, et al. Cyclic peptides from the opportunistic pathogen basidiobolus meristosporus. J Nat Prod. 2023;86:1885–90.

  8. Huang RF, Zhou RH, Zhou SF, Lin HX, Lu SS, Qiu JN, et al. New sesquiterpene from a soil fungus of Trichoderma sp. Nat Prod Res. 2024;38:1562–9.

    Article  CAS  PubMed  Google Scholar 

  9. Yang G, Wang JY, Lu SS, Chen Z, Fan S, Chen DW, et al. Short lipopeptides specifically inhibit the growth of Propionibacterium acnes with a dual antibacterial and anti-inflammatory action. Br J Pharm. 2019;176:2321–35.

    Article  CAS  Google Scholar 

  10. Karadogan B, Parsons PJ. Synthesis of racemic brevioxime and related analogues. Tetrahedron. 2001;57:8699–703.

    Article  CAS  Google Scholar 

  11. Maejima Y, Nakatsugawa H, Ichida D, Maejima M, Aoyagi Y, Maoka T, et al. Functional compounds in fermented buckwheat sprouts. Biosci Biotechnol Biochem. 2011;75:1708–12.

    Article  CAS  PubMed  Google Scholar 

  12. Wang WC, Xia YM, Yang B, Su XN, Chen JK, Li W, et al. Protective effects of tyrosol against lPS-induced acute lung injury via inhibiting NF-κB and AP-1 activation and activating the HO-1/Nrf2 pathways. Biol Pharm Bull. 2017;40:583–93.

    Article  CAS  PubMed  Google Scholar 

  13. Kumar N, Mohandas C, Nambisan B, Kumar DRS, Lankalapalli RS. Isolation of proline-based cyclic dipeptides from Bacillus sp. strain associated with rhabitid entomopathogenic nematode and its antimicrobial properties. World J Microbiol Biotechnol. 2013;29:355–64.

    Article  CAS  PubMed  Google Scholar 

  14. Smaoui S, Mathieu F, Elleuch L, Coppel Y, Merlina G, Karray-Rebai I, et al. Taxonomy, purification and chemical characterization of four bioactive compounds from new Streptomyces sp TN256 strain. World J Microbiol Biotechnol. 2012;28:793–804.

    Article  CAS  PubMed  Google Scholar 

  15. Li DD, Wang Y, Kim EL, Hong J, Jung JH. Neuroprotective efect of cyclo-(L-Pro-L-Phe) isolated from the jellyfish-derived fungus Aspergillus flavus. Mar Drugs. 2021;19:417.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ran Y, Zhang Y, Wang X, Li GH. Nematicidal metabolites from the actinomycete Micromonospora sp. WH06. Microorganisms. 2022;10:2274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Guo JP, Tan JL, Wang YL, Wu HY, Zhang CP, Niu XM, et al. Isolation of talathermophilins from the thermophilic fungus Talaromyces thermophilus YM3-4. J Nat Prod. 2011;74:2278–81.

    Article  CAS  PubMed  Google Scholar 

  18. Qi JZ, Han HY, Sui D, Tan SN, Liu CL, Wang PC, et al. Efficient production of a cyclic dipeptide (cyclo-TA) using heterologous expression system of filamentous fungus Aspergillus oryzae. Microb Cell Fact. 2022;21:146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bhushan R, Brückner H. Marfey’s reagent for chiral amino acid analysis: a review. Amino Acids. 2004;27:231–47.

    Article  CAS  PubMed  Google Scholar 

  20. Li ZC. Cholesterol as a chiral auxiliary for the synthesis of D-biotin key intermediate-lactone. Chem Eng Equip. 2009;01:3–8.

  21. Driche EH, Badji B, Bijani C, Belghit S, Pont F, Mathieu F, et al. Antibacterial and antibiofilm properties of two cyclic dipeptides produced by a new desert Streptomyces sp. HG-17 strain against multidrug-resistant pathogenic bacteria. Int Microbiol. 2024;28:41–255.

  22. Jha NK, Kumar LL, Sivasankar C, Gopu V, Devi PB, Murali A, et al. Cyclic di-peptide Cyclo (L-Phe-L-Pro) mitigates the quorum-sensing mediated virulence in Salmonella typhi and biofilm formation in poultry and plastic system. Food Biosci. 2024;60:104391.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the funding from the National Natural Science Foundation of China (81773556), Science and Technology Department of Guangdong Province of China (2022A1515010182 and 2023A1515012933), and Southern Medical University (B1040903).

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  1. Group of Peptides and Natural Products Research, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China

    Shuaiqi Ma, Shixin Li, Li Song, Asma Riaz, Ruifeng Huang, Shaofen Zhou, Jingnan Qiu, Zonglin Chu & Jian He

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  1. Shuaiqi Ma
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Correspondence to Jian He.

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Ma, S., Li, S., Song, L. et al. Isolation and synthesis of a new cyclic tetrapeptide from marine-associated Bacillus sp. and its bacterial biofilm formation inhibitory activity. J Antibiot 78, 408–417 (2025). https://doi.org/10.1038/s41429-025-00830-x

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