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Substrate and inhibitor selectivity, and biological activity of an epoxide hydrolase from Trichoderma reesei

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Abstract

Epoxide hydrolases (EHs) are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EH are involved in the metabolism of endogenous and exogenous epoxides, and thus have application in pharmacology and biotechnology. In this work, we describe the substrates and inhibitors selectivity of an epoxide hydrolase recently cloned from the filamentous fungus Trichoderma reesei QM9414 (TrEH). We also studied the TrEH urea-based inhibitors effects in the fungal growth. TrEH showed high activity on radioative and fluorescent surrogate and natural substrates, especially epoxides from docosahexaenoic acid. Using a fluorescent surrogate substrate, potent inhibitors of TrEH were identified. Interestingly, one of the best compounds inhibit up to 60% of T. reesei growth, indicating an endogenous role for TrEH. These data make TrEH very attractive for future studies about fungal metabolism of fatty acids and possible development of novel drugs for human diseases.

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Acknowledgements

This work was supported by National Institute of Environmental Health Sciences (Grant No. NIEHS-R01 ES002710), the Superfund Program NIEHS (Grant No. P42 ES 04699), and São Paulo Research Foundation (Grant Nos. FAPESP-2014/24107-1, 2017/25705-8). G.S.O. and P.P.A. is supported by a scholarship from FAPESP (Grant Nos. 2015/03329-9 and 2016/12859-4) and CNPq (142311/2016-2), respectively.

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Authors and Affiliations

  1. Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, 1000 Av. Arlindo Bettio, Ermelino Matarazzo, CEP: 03828-000, São Paulo, Brazil

    Gabriel S. de Oliveira, Patricia P. Adriani & Felipe S. Chambergo

  2. Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, One Shields Avenue, Davis, CA, USA

    Hao Wu, Christophe Morisseau & Bruce D. Hammock

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  1. Gabriel S. de Oliveira
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  2. Patricia P. Adriani
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  3. Hao Wu
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  4. Christophe Morisseau
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  5. Bruce D. Hammock
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  6. Felipe S. Chambergo
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Correspondence to Felipe S. Chambergo.

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de Oliveira, G.S., Adriani, P.P., Wu, H. et al. Substrate and inhibitor selectivity, and biological activity of an epoxide hydrolase from Trichoderma reesei. Mol Biol Rep 46, 371–379 (2019). https://doi.org/10.1007/s11033-018-4481-4

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