Journal of Microbiology

, Volume 52, Issue 1, pp 64–70 | Cite as

Cyclic dipeptides from lactic acid bacteria inhibit the proliferation of pathogenic fungi

  • Min-Kyu Kwak
  • Rui Liu
  • Min-Kyu Kim
  • Dohyun Moon
  • Andrew HyoungJin Kim
  • Sung-Hyun Song
  • Sa-Ouk KangEmail author
Microbial Physiology and Biochemistry


Lactobacillus plantarum LBP-K10 was identified to be the most potent antifungal strain from Korean traditional fermented vegetables. The culture filtrate of this strain showed remarkable antifungal activity against Ganoderma boninense. Five fractions from the culture filtrate were observed to have an inhibitory effect against G. boninense. Also, the electron ionization and chemical ionization indicated that these compounds might be cyclic dipeptides. Of the five active fractions, two fractions showed the most significant anti-Ganoderma activity, and one of these fractions inhibited the growth of Candida albicans. These compounds were identified to be cis-cyclo(l-Val-l-Pro) and cis-cyclo(l-Phe-l-Pro), as confirmed by X-ray crystallography.


Lactobacillus plantarum LBP-K10 culture filtrate, cis-cyclo(l-Val-l-Pro) cis-cyclo(l-Phe-l-Pro) Ganodermaboninense Candida albicans 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abee, T., Krockel, L., and Hill, C. 1995. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning. Int. J. Food. Microbiol. 28, 169–185.PubMedCrossRefGoogle Scholar
  2. Bivi, M.R., Farhana, M.S.N., Khairulmazmi, A., and Idris, A. 2010. Control of Ganoderma boninense: A causal agent of basal stem rot disease in oil palm with endophyte bacteria in vitro. Int. J. Agric. Biol. 12, 833–839.Google Scholar
  3. Budesinsky, M., Cisarova, I., Podlaha, J., Borremans, F., Martins, J.C., Waroquier, M., and Pauwels, E. 2010. Structures of cyclic dipeptides: an X-ray and computational study of cis- and trans-cyclo(Pip-Phe), cyclo(Pro-Phe) and their N-methyl derivatives. Acta Crystallogr. B. 66, 662–677.PubMedCrossRefGoogle Scholar
  4. Chong, K.P., Rossall, S., and Atong, M. 2009. In vitro antimicrobial activity and fungitoxicity of syringic acid, caffeic acid and 4-hydroxybenzoic acid against Ganoderma Boninense. J. Agr. Sci. 1, 15–20.Google Scholar
  5. Gänzle, M.G., Höltzel, A., Walter, J., Jung, G., and Hammes, W.P. 2000. Characterization of reutericyclin produced by Lactobacillus reuteri LTH2584. Appl. Environ. Microbiol. 66, 4325–4333.PubMedCentralPubMedCrossRefGoogle Scholar
  6. Gibson, G.R., Saavedra, J.M., MsFarlane, S., and McFarlane, G.T. 1997. Probiotics and intestinal infections. In Fuller, R. (ed.) Probiotics 2: Applications and practical aspects, pp. 10–39. Chapman & Hall, New York, N.Y., USA.CrossRefGoogle Scholar
  7. Graz, M., Hunt, A., Jamie, H., Grant, G., and Milne, P. 1999. Antimicrobial activity of selected cyclic dipeptides. Pharmazie 54, 772–775.PubMedGoogle Scholar
  8. Havenaar, R., Brink, B., and Huis in’t Veld, J.H.J. 1992. Selection of strains for probiotic use. In Fuller. R. (ed.). Probiotics, the scientific basis, pp. 209–224. Chapman and Hall, London, USA.Google Scholar
  9. Holzapfel, W.H., Haberer, P., Geisen, R., Björkroth, J., and Schillinger, U. 2001. Taxonomy and important features of probiotic microorganisms in food and nutrition. Am. J. Clin. Nutr. 73, 365S–373S.PubMedGoogle Scholar
  10. Kwak, M.K., Liu, R., Kwon, J.O., Kim, M.K., Kim, A.H., and Kang, S.O. 2013. Cyclic dipeptides from lactic acid bacteria inhibit proliferation of the influenza A virus. J. Microbiol. 51, 836–843.CrossRefGoogle Scholar
  11. Lee, K.H., Kim, K.W., and Rhee, K.H. 2010. Identification of Streptomyces sp. KH29, which produces an antibiotic substance processing an inhibitory activity against multidrug-resistant Acinetobacter baumannii. J. Microbiol. Biotechnol. 20, 1672–1676.PubMedGoogle Scholar
  12. Li, H., Liu, L., Zhang, S., Cui, W., and Lv, J. 2012. Identification of antifungal compounds produced by Lactobacillus casei AST18. Curr. Microbiol. 65, 156–161.PubMedCrossRefGoogle Scholar
  13. Mayo, B., van Sinderen, D., and Ventura, M. 2008. Genome analysis of food grade lactic acid-producing bacteria: from basics to applications. Curr. Genomics 9, 169–183.PubMedCrossRefGoogle Scholar
  14. McCleland, K., Milne, P.J., Lucieto, F.R., Frost, C., Brauns, S.C., Van De Venter, M., Du Plessis, J., and Dyason, K. 2004. An investigation into the biological activity of the selected histidine-containing diketopiperazines cyclo(His-Phe) and cyclo(His-Tyr). J. Pharm. Pharmacol. 56, 1143–1153.PubMedCrossRefGoogle Scholar
  15. Magnusson, J., Ström, K., Roos, S., Sjögren, J., and Schnürer, J. 2003. Broad and complex antifungal activity among environmental isolates of lactic acid bacteria. FEMS Microbiol. Lett. 219, 129–135.PubMedCrossRefGoogle Scholar
  16. Nardi, R.M., Santoro, M.M., Oliveira, J.S., Pimenta, A.M., Ferraz, V.P., Benchetrit, L.C., and Nicoli, J.R. 2005. Purification and molecular characterization of antibacterial compounds produced by Lactobacillus murinus strain L1. J. Appl. Microbiol. 99, 649–656.PubMedCrossRefGoogle Scholar
  17. Niku-Paavola, M.L., Laitila, A., Mattila-Sandholm, T., and Haikara, A. 1999. New types of antimicrobial compounds produced by Lactobacillus plantarum. J. Appl. Microbiol. 86, 29–35.PubMedCrossRefGoogle Scholar
  18. O’Neill, J.C. and Blackwell, H.E. 2007. Solid-phase and microwave-assisted syntheses of 2,5-diketopiperazines: small molecules with great potential. Comb. Chem. High Throughput Screen. 10, 857–876.PubMedCentralPubMedCrossRefGoogle Scholar
  19. Pilotti, C.A., Sanderson, F.R., Aitken, E.A., and Armstrong, W. 2004. Morphological variation and host range of two Ganoderma species from Papua New Guinea. Mycopathologia 158, 251–265.PubMedCrossRefGoogle Scholar
  20. Pilotti, C.A. 2005. Stem rots of oil palm caused by Ganoderma boninense: pathogen biology and epidemiology. Mycopathologia 159, 129–137.PubMedCrossRefGoogle Scholar
  21. Prasad, C. 1995. Bioactive cyclic dipeptides. Peptides 16, 151–164.PubMedCrossRefGoogle Scholar
  22. Rees, R.W., Flood, J., Hasan, Y., and Cooper, R.M. 2007. Effects of inoculum potential, shading and soil temperature on root infection of oil palm seedlings by the basal stem rot pathogen Ganoderma boninense. Plant Pathol. 56, 862–870.CrossRefGoogle Scholar
  23. Rhee, K.H. 2004. Cyclic dipeptides exhibit synergistic, broad spectrum antimicrobial effects and have anti-mutagenic properties. Int. J. Antimicrob. Agents 24, 423–427.PubMedCrossRefGoogle Scholar
  24. Sherman, F. 2002. Getting started with yeast. Methods Enzymol. 350, 3–41.PubMedGoogle Scholar
  25. Ström, K., Sjögren, J., Broberg, A., and Schnürer, J. 2002. Lactobacillus plantarum MiLAB 393 produces the antifungal cyclic dipeptides cyclo(l-Phe-l-Pro) and cyclo(l-Phe-trans-4-OH-l-Pro) and 3-phenyllactic acid. Appl. Environ. Microbiol. 68, 4322–4327.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Saavedra, J.M. 1995. Microbes to fight microbes: a not so novel approach to controlling diarrheal disease. J. Pediatr. Gastroenterol. Nutr. 21, 125–129.PubMedCrossRefGoogle Scholar
  27. Trabocchi, A., Scarpi, D., and Guarna, A. 2008. Structural diversity of bicyclic amino acids. Amino Acids 34, 1–24.PubMedCrossRefGoogle Scholar
  28. Wang, H., Yan, Y., Wang, J., Zhang, H., and Qi, W. 2012. Production and characterization of antifungal compounds produced by Lactobacillus plantarum IMAU10014. PLoS One 7, e29452.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Min-Kyu Kwak
    • 1
  • Rui Liu
    • 1
  • Min-Kyu Kim
    • 1
  • Dohyun Moon
    • 2
  • Andrew HyoungJin Kim
    • 1
  • Sung-Hyun Song
    • 1
  • Sa-Ouk Kang
    • 1
    Email author
  1. 1.Laboratory of Biophysics, School of Biological Sciences, and Institute of MicrobiologySeoul National UniversitySeoulRepublic of Korea
  2. 2.Beamline Division, X-ray Research II Team at Pohang Accelerator LaboratoryPOSTECHPohangRepublic of Korea

Personalised recommendations