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Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus

  • Short Communication
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

The biotransformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus MT 5.3 yielded a rare derivative that was elucidated by spectrometric methods. The fungus led to the formation of a different product through an unusual epoxidation reaction between C4 and C5, formation of a C3,C10 ether bridge, and a methoxylation of the C1 of tagitinin C. The chemical structure of the product, namely 1β-methoxy-3α-hydroxy-3,10β-4,5α-diepoxy-8β-isobutyroyloxygermacr-11(13)-en-6α,12-olide, is the same as that of a derivative that was recently isolated from the flowers of a Brazilian population of Mexican sunflower (Tithonia diversifolia), which is the source of the substrate tagitinin C. The in vitro cytotoxic activity of the substrate and the biotransformed product were evaluated in HL-60 cells using an MTT assay, and both compounds were found to be cytotoxic. We show that soil fungi may be useful in the biotransformation of sesquiterpene lactones, thereby leading to unusual changes in their chemical structures that may preserve or alter their biological activities, and may also mimic plant biosynthetic pathways for production of secondary metabolites.

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Fig. 1

Abbreviations

DAD:

Diode array detector

HPLC:

High-performance liquid chromatography

HR-ESIMS:

High-resolution electrospray ionisation mass spectrometry

MeCN:

Acetonitrile

MeOH:

Methanol

NMR:

Nuclear magnetic resonance

STL:

Sesquiterpene lactone(s)

TLC:

Thin-layer chromatography

UV:

Ultraviolet

References

  1. Aleu J, Hanson JR, Galan RH, Collado IG (1999) Biotransformation of the fungistatic sesquiterpenoid patchoulol by Botrytis cinerea. J Nat Prod 62:437–440

    Article  PubMed  CAS  Google Scholar 

  2. Ambrósio SR, Oki Y, Heleno VCGH, Chaves JS, Nascimento PGBD, Lichston JE, Constantino MG, Varanda EM, Da Costa FB (2008) Constituents of glandular trichomes of Tithonia diversifolia: relationships to herbivory and antifeedant activity. Phytochemistry 69:2052–2060

    Article  PubMed  Google Scholar 

  3. Ata A, Nachtigall JA (2004) Microbial transformations of α-santonin. Z Naturforsch 59c:209–214

    Google Scholar 

  4. Avery MA, Alvim-Gaston M, Rodriguez CR, Barriero EJ, Cohen FE, Sabnis YA, Woolfrey JR (2002) Structure–activity relationships of the antimalarial agent artemisinin 6: the development of predictive in vitro potency models using COMFA and HQSAR methodologies. J Med Chem 45:292–303

    Article  PubMed  CAS  Google Scholar 

  5. Barrero AF, Oltra JE, Alvarez M, Raslan DS, Saúde DA, Akssira M (2000) New sources and antifungal activity of sesquiterpene lactones. Fitoterapia 71:60–64

    Article  PubMed  CAS  Google Scholar 

  6. Barrero AF, Oltra JE, Raslan DS, Saúde DA (1999) Microbial transformation of sesquiterpene lactones by the fungi Cunninghamella echinulata and Rhizopus oryzae. J Nat Prod 62:726–729

    Article  PubMed  CAS  Google Scholar 

  7. Borges WS, Borges KB, Bonato PS, Pupo MT (2009) Endophytic fungi: natural products, enzymes and biotransformation reactions. Curr Org Chem 13:1137–1163

    Article  CAS  Google Scholar 

  8. Chagas-Paula DA, Oliveira RB, Silva VC, Gobbo-Neto L, Gasparoto TH, Campanelli AP, Faccioli LH, Da Costa FB (2011) Chlorogenic acids from Tithonia diversifolia demonstrate better anti-inflammatory effect than indomethacin and its sesquiterpene lactones. J Ethnopharmacol 136:355–362

    Article  PubMed  CAS  Google Scholar 

  9. Coll JC, Bowden BF (1986) The application of vacuum liquid chromatography to the separation of terpene mixtures. J Nat Prod 49:934–936

    Article  CAS  Google Scholar 

  10. Da Costa FB, Terfloth L, Gasteiger J (2005) Sesquiterpene lactone-based classification of three Asteraceae tribes: a study based on self-organizing neural networks applied to chemosystematics. Phytochemistry 66:345–353

    Article  PubMed  Google Scholar 

  11. Galal AM, Ibrahim AS, Mossa JS, El Feraly FS (1999) Microbial transformation of parthenolide. Phytochemistry 51:761–765

    Article  CAS  Google Scholar 

  12. Gładkowski W, Grabarczyk M, Winska K, Ratus B, Białonska A, Ciunik Z (2007) Lactones 26: stereoselective microbial epoxidation of unsaturated bicyclic γ-lactones with the alkylsubstituted cyclohexane system. J Mol Catal B Enzym 49:79–87

    Article  Google Scholar 

  13. Hashimoto T, Noma Y, Asakawa Y (2001) Biotransformation of terpenoids from the crude drugs and animal origin by microorganisms. Heterocycles 54:529–559

    Article  CAS  Google Scholar 

  14. Heinrich M, Robles M, West JE, Montellano BR, Rodriguez E (1998) Ethnopharmacology of Mexican Asteraceae (Compositae). Annu Rev Pharmacol Toxicol 38:539–565

    Article  PubMed  CAS  Google Scholar 

  15. Kim HJ, Park H, Lee I (2006) Microbial transformation of silybin by Trichoderma koningii. Bioorg Med Chem Lett 16:790–793

    Article  PubMed  CAS  Google Scholar 

  16. Kouzi SA, McChesney JD (1991) Microbial models of mammalian metabolism: fungal metabolism of diterpene sclareol by Cunninghamella species. J Nat Prod 54:483–490

    Article  PubMed  CAS  Google Scholar 

  17. Krishna-Kumari GN, Masilamani S, Ganesh MR, Aravind S (2003) Microbial transformation of zaluzanin-D. Phytochemistry 62:1101–1104

    Article  Google Scholar 

  18. Kupchan SM, Eakin MA, Thomas AM (1971) Tumor inhibitors: structure–cytotoxicity relations among the sesquiterpene lactones. J Med Chem 14:1147–1152

    Article  PubMed  CAS  Google Scholar 

  19. Kuroda M, Yokosuka R, Kobayashi R, Jitsuno H, Kando H, Nosaka K, Ishi H, Yamori T, Mimaki Y (2007) Sesquiterpenoids and flavonoids from the aerial parts of Tithonia diversifolia and their cytotoxic activity. Chem Pharm Bull 55:1240–1244

    Article  PubMed  CAS  Google Scholar 

  20. Lamare V, Furtoss R (1990) Bioconversion of sesquiterpenes. Tetrahedron 12:4109–4132

    Article  Google Scholar 

  21. Liu JH, Chen YG, Yu BY, Chen YJ (2006) A novel ketone derivative of artemisin in biotransformed by Streptomyces griseus ATCC 13273. Bioorg Med Chem Lett 16:1909–1921

    Article  PubMed  CAS  Google Scholar 

  22. Ma X, Ye M, Wu L, Guo D (2006) Microbial transformation of curdione by Mucor spinosus. Enzyme Microb Technol 38:367–371

    Article  CAS  Google Scholar 

  23. Mossman BT (1983) In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts. Environ Health Perspect 53:155–161

    Article  PubMed  CAS  Google Scholar 

  24. Musharraf SG, Najeeb A, Khan S, Pervez M, Ali RA, Choudhary MI (2010) Microbial transformation of 5α-hydroxycaryophylla-4(12),8(13)-diene with Macrophomina phaseolina. J Mol Catal B Enzym 66:156–160

    Article  CAS  Google Scholar 

  25. Nasim S, Crooks PA (2008) Antileukemic activity of aminoparthenolide analogs. Bioorg Med Chem Lett 18:3870–3873

    Article  PubMed  CAS  Google Scholar 

  26. Onken J, Berger RG (1999) Biotransformation of citronellol by the basidiomycete Cystoderma carcharias in an aerated-membrane bioreactor. Appl Microbiol Biotechnol 51:158–163

    Article  PubMed  CAS  Google Scholar 

  27. Orabi KY, Galal AM, Ibrahim AS, El-Feraly FS, Khalifa SI, El Sohly HN (1999) Microbial metabolism of artemisitene. Phytochemistry 51:257–261

    Article  PubMed  CAS  Google Scholar 

  28. Parshikov IA, Miriyala B, Muraleedharan KM, Avery MA, Williamson JS (2006) Microbial transformation of artemisinin to 5-hydroxyartemisinin by Eurotium amstelodami and Aspergillus niger. J Ind Microbiol Biotechnol 33:349–352

    Article  PubMed  CAS  Google Scholar 

  29. Parshikov IA, Netrusov AI, Sutherland JB (2012) Microbial transformation of antimalarial terpenoids. Biotechnol Adv. doi:10.1016/j.biotechadv.2012.03.010

  30. Passreiter CM, Isman MB (1997) Antifeedant bioactivity of sesquiterpene lactones from Neurolaena lobata and their antagonism by γ-aminobutyric acid. Biochem Syst Ecol 25:371–375

    Article  CAS  Google Scholar 

  31. Rahman A, Farooq A, Choudhary MI (1997) Microbial transformation of sclareolide. J Nat Prod 60:1038–1040

    Article  Google Scholar 

  32. Rodriguez E, Towers GHN, Mitchell JC (1976) Biological activities of sesquiterpene lactones. Phytochemistry 15:1573–1580

    Article  CAS  Google Scholar 

  33. Rüngeler P, Lyss G, Castro V, Mora G, Pahl HL, Merfort I (1998) Study of three sesquiterpene lactones from Tithonia diversifolia on their anti-inflammatory activity using the transcription factor NF-κB and enzymes of the arachidonic acid pathway as targets. Planta Med 64:588–593

    Article  PubMed  Google Scholar 

  34. Sanchez-Gonzalez M, Rosazza JPN (2004) Microbial transformations of chalcones: hydroxylation, O-demethylation and cyclization to flavanones. J Nat Prod 67:553–558

    Article  PubMed  CAS  Google Scholar 

  35. Schmidt TJ (1999) Toxic activities of sesquiterpene lactones: structural and biochemical aspects. Curr Org Chem 3:577–582

    CAS  Google Scholar 

  36. Schmidt TJ, Heilmann J (2002) Quantitave structure-cytotoxicity relationships of sesquirtepene lactones derived from partial charge (Q)-based fractional accessible surface area descriptors (Q_fr SAs). Quant Struct-Act Relat 21:276–287

    Article  Google Scholar 

  37. Seaman FC (1982) Sesquiterpene lactones as taxonomic characters in the Asteraceae. Bot Rev 48:121–595

    Article  CAS  Google Scholar 

  38. Spring O, Zipper R, Reeb S, Vogler B, Da Costa FB (2001) Sesquiterpene lactones and a myoinositol from glandular trichomes of Viguiera quinqueremis. Phytochemistry 57:267–272

    Article  PubMed  CAS  Google Scholar 

  39. Zhan J, Zhang Y, Guo H, Han J, Ning L, Guo D (2002) Microbial metabolism of artemisin by Mucor polymorphosporus and Aspergillus niger. J Nat Prod 65:1693–1695

    Article  PubMed  CAS  Google Scholar 

  40. Zhang J, Guo H, Tian Y, Liu P, Li N, Zhou J, Guo D (2007) Biotransformation of 20(S)-protopanaxatriol by Mucor spinosus and the cytotoxic structure activity relationships of the transformed products. Phytochemistry 68:2523–2530

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors acknowledge Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP–Bioprospecta/Biota–process # 04/07935-6), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support, and Prof. N. A. J. C. Furtado (FCFRP-USP) for technical support.

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Authors and Affiliations

  1. Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (FCFRP-USP), Av. do Café s/no., Ribeirão Preto, SP, 14040-903, Brazil

    Bruno Alves Rocha, Mônica Tallarico Pupo, Suraia Said & Fernando Batista Da Costa

  2. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, FCFRP-USP, Ribeirão Preto, SP, Brazil

    Gilmara Ausech Antonucci, Suely Vilela Sampaio & Raquel de Melo Alves Paiva

  3. Departamento de Física e Química, FCFRP-USP, Ribeirão Preto, SP, Brazil

    Leonardo Gobbo-Neto

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  1. Bruno Alves Rocha
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  2. Mônica Tallarico Pupo
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  3. Gilmara Ausech Antonucci
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Correspondence to Fernando Batista Da Costa.

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Rocha, B.A., Pupo, M.T., Antonucci, G.A. et al. Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus . J Ind Microbiol Biotechnol 39, 1719–1724 (2012). https://doi.org/10.1007/s10295-012-1165-2

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  • DOI: https://doi.org/10.1007/s10295-012-1165-2

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