Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Enhancement of a pentacyclic tyrosine kinase inhibitor production in Cladosporium cf. cladosporioides by Cladosporol

  • 105 Accesses

  • 4 Citations

Abstract

The binaphthyl derivative cladosporol 3 was supplied from 60 to 200 mg l−1 to shaken cultures of Cladosporium cf. cladosporioides. Compared to blank, fungal biomass was not affected by adding cladosporol till 100 mg l−1: it rather increased at higher ratios between 150 and 200 mg l−1. The production of the major pentacyclic metabolite 1, a cytokine production and tyrosine kinase inhibitor, was enhanced tenfold when cladosporol was supplied at the highest ratio (200 mg l−1) to shaken growing cultures of the fungus. The bioconversion of cladosporol to cladosporol D through reductive cleavage of the epoxide group was also observed. Interest in this kind of metabolites lies in their potential activity vs DNA topoisomerase I.

This is a preview of subscription content, log in to check access.

Scheme 1
Fig. 1

References

  1. Arnone A, Assante G, Merlini L, Nasini G (1989) Structure and stereochemistry of Cladochrome D and E, novel perylenequinone pigments from C. cladosporioides. Gazz Chim Ital 119:557–559

  2. Assante G, Maffi D, Saracchi M, Farina G, Moricca S, Ragazzi A (2004) Hystological studies on the mycoparasitism of Cladosporium tenuissimum and urediniospores of Uromyces appendiculatus. Mycol Res 108:170–182

  3. Brauers G, Ebel R, Edrada R, Wray V, Berg A, Gräfe U, Proksch P (2001) Hortein, a new natural product from the fungus Hortaea werneckii associated with the sponge Aplysina aerophoba. J Nat Prod 64:651–652

  4. Edwards RL, Lockett HJ (1976) Constituents of higher fungi. Part XVI. Bulgarhodin and bulgarein, novel benzofluoranthenequinones from the fungus Bulgaria inquinans. J Chem Soc, Perkin Trans I 2149–2155

  5. Fujii N, Yamashita Y, Saitoh Y, Nakano H (1993) Induction of mammalian DNA topoisomerase I-mediated DNA cleavage and DNA winding by bulgarein. J Biol Chem 268:13160–13165

  6. Koyama K, Kuramochi D, Kinoshita K, Takahashi K (2002) Hypoxylonols A and B, novel reduced benzo[j]fluoranthene derivatives from the mushroom Hypoxylon truncatum. J Nat Prod 65:1489–1490

  7. Liu LF (1994) DNA topoisomerases: biochemistry and molecular biology. Advances in Pharmacology, vol 29A, Academic Press, New York, USA, p 320

  8. Moricca S, Ragazzi A, Mitchelson KR, Assante G (2001) Antagonism of the two-needle pine stem rust fungi Cronartium flaccidum and Peridermium pini by Cladosporium tenuissimum in vitro and in planta. Phytopathology 91:457–468

  9. Nasini G, Arnone A, Assante G, Bava A, Moricca S, Ragazzi A (2004) Secondary mould metabolites of Cladosporium tenuissimum, a hyperparasite rust fungi. Phytochemistry 65:2107–2111

  10. Quang DN, Hashimoto T, Tanaka M, Baumgartner M, Stadler M, Asakawa Y (2002) Chemical constituents of the Ascomycete Daldinia concentrica. J Nat Prod 65:1869–1874

  11. Sakagami Y, Sano A, Hara O, Mikawa T, Marumo S (1995) Cladosporol, β-1,3-glucan biosynthesis inhibitor, isolated by the fungus Cladosporium cladosporioides. Tetrahedron Lett 36:1469–1472

  12. Tamaoki T, Nakano H (1990) Potent and specific inhibitors of protein kinase C of microbial origin. Bio/Technology 8:732–735

  13. Weiss U, Merlini L, Nasini G (1987) Naturally occurring perylenequinones. Progress in the chemistry of organic natural products, vol 57, Springer, Wien, pp 1–71

  14. Wrigley SK, Ainsworth AM, Kau DA, Martin SM, Bahl S, Tang JS, Hardick DJ, Rawlins P, Sadheghi R, Moore M (2001) Novel reduced benzo[j]fluoranthen-3-ones from Cladosporium cf. cladosporioides with cytokine production and tyrosine kinase inhibitory properties. J Antibiot 54:479–488

Download references

Acknowledgements

This work was in part supported by a Grant of MIUR-FIRB (Italy). Thanks are due to Prof. Wrigley and his collaborators for the C. cladosporioides culture and helpful discussion on results.

Author information

Correspondence to Gemma Assante.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Assante, G., Bava, A. & Nasini, G. Enhancement of a pentacyclic tyrosine kinase inhibitor production in Cladosporium cf. cladosporioides by Cladosporol. Appl Microbiol Biotechnol 69, 718–721 (2006). https://doi.org/10.1007/s00253-005-0054-2

Download citation

Keywords

  • Biotransformation
  • Cladosporium
  • Reductive Cleavage
  • Binaphthyl
  • Specific Cell Activity