Increasing chemical diversity through biotransformation of terpenoids by fungi

Fungi comprise an efficient and cost-effective alternative to generate new chemical compounds that are not easily obtained by classical organic synthesis. Therefore these organisms are effective in increasing the chemical diversity so that new derivatives with lower toxicity or improved biological activity can be obtained [1].

The sesquiterpene lactone budlein A is a furanoheliangolide that is found in high amounts in Brazilian sunflower-like plants from the genusViguiera (Asteraceae). It has important biological effects like potent cytotoxic activity against the human leukemic cell line HL-60 as well as in vitro and in vivo anti-inflammatory effect [2,3]. Due to the fact that budlein A may have toxic properties and the obtention of synthetic analogues is quite complex, we screened several fungi that could produce new derivatives. In this work, we report the biotransformation of budlein A by the soil fungi Aspergillus terreus and A. niger. The organic layer obtained from the culture filtrates in Czapeck medium was chromatographed over silica gel and the products were purified by HPLC. The structures were elucidated by NMR spectrometry and HRESIMS. Important modifications of the sesquiterpenoid core structure by the fungi resulted in three new and unusual products. The two compounds transformed by A. terreus lack the lactone ring and that transformed by A. niger has an aromatic moiety attached to the sesquiterpene ring. All derivatives presented a reduced cytotoxicity against HL-60 cells compared to the original natural product, which is more potent than the positive control cisplatin. Our results show the versatility of microbial-catalyzed biotransformations leading to unusual derivatives with pharmacological interest.

Acknowledgements: FAPESP, CNPq, CAPES.

References: 1. Müller, M. (2004) Curr. Opin. Chem. Biol. 15: 591–598.

2. Arakawa, N.S. et al. (2008) Z. Naturforsch. C 63, in press.

3. Valério, D.A.R. et al. (2007) Eur. J. Pharmacol. 562: 155–163.