Review

Fungal homoserine transacetylase: A potential antifungal target

Volume: 51 Number: 1 April 30, 2021
  • Esra Seyran

Fungal homoserine transacetylase: A potential antifungal target

Abstract

We are facing a significant challenge due to the tremendous rise in drug resistant fungal pathogen populations. The number of antifungal drugs is limited, as are the known targets they inhibit. The limited number of drugs and targets that have been successfully exploited in antifungal drug discovery is in part due to the eukaryotic nature of these organisms, which is shared with mammalian cells. An ideal antifungal substance is one that targets an indispensable pathway for pathogenic fungal survival that is not present in mammals or plants. Methionine is an essential amino acid for fungi and inhibition of its biosynthesis is deleterious for the pathogen. The biochemical pathways that produce methionine do not exist in mammals as they acquire it from their diet. Homoserine transacetylase, which catalyses the first committed step in methionine biosynthesis, therefore represents an attractive drug target. This enzyme is absent in mammals and unique to fungi and bacteria, suggesting that drugs targeting it would be of low toxicity, if any, to mammals, while having a lethal effect against the fungal pathogen. Homoserine transacetylase, based on its role in the production of methionine and its absence in mammals and plants could be a potential antifungal target.

Keywords

References

  1. • Ashman, R. B., Farah, C. S., Wanasaengsakul, S., Hu, Y., Pang, G., & Clancy, R. L. (2004). Innate versus adaptive immunity in Candida albicans infection. Immunology and Cell Biology, 82(2), 196–204. https://doi.org/10.1046/j.0818-9641.2004.01217.x
  2. • Born, T. L., Franklin, M., & Blanchard, J. S. (2000). Enzyme-catalyzed acylation of homoserine: mechanistic characterization of the Haemophilus influenzae met2-encoded homoserine transacetylase. Biochemistry, 39(29), 8556–8564. https://doi.org/10.1021/ bi000462p
  3. • Chang, Y. L., Yu, S. J., Heitman, J., Wellington, M., & Chen, Y. L. (2017). New facets of antifungal therapy. Virulence, 8(2), 222–236. https://doi.org/10.1080/21505594.2016.1257457
  4. • Cleland W. W. (1977). Determining the chemical mechanisms of enzyme-catalyzed reactions by kinetic studies. Advances in Enzymology and Related Areas of Molecular Biology, 45, 273–387. https://doi.org/10.1002/9780470122907.ch4
  5. • Hollomon D. W. (1993). Resistance to azole fungicides in the field. Biochemical Society Transactions, 21(4), 1047–1051. https:// doi.org/10.1042/bst0211047
  6. • Low, C. Y., & Rotstein, C. (2011). Emerging fungal infections in immunocompromised patients. F1000 Medicine Reports, 3, 14. https://doi.org/10.3410/M3-14
  7. • Mazu, T. K., Bricker, B. A., Flores-Rozas, H., & Ablordeppey, S. Y. (2016). The Mechanistic Targets of Antifungal Agents: An Overview. Mini Reviews in Medicinal Chemistry, 16(7), 555–578. https:// doi.org/10.2174/1389557516666160118112103
  8. • Nazi, I., & Wright, G. D. (2005). Catalytic mechanism of fungal homoserine transacetylase. Biochemistry, 44(41), 13560–13566. https://doi.org/10.1021/bi0514764

Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences, Health Care Administration

Journal Section

Review

Authors

Publication Date

April 30, 2021

Submission Date

July 19, 2020

Acceptance Date

September 4, 2020

Published in Issue

Year 2021 Volume: 51 Number: 1

APA
Seyran, E. (2021). Fungal homoserine transacetylase: A potential antifungal target. İstanbul Journal of Pharmacy, 51(1), 137-140. https://izlik.org/JA38LU43RC
AMA
1.Seyran E. Fungal homoserine transacetylase: A potential antifungal target. iujp. 2021;51(1):137-140. https://izlik.org/JA38LU43RC
Chicago
Seyran, Esra. 2021. “Fungal Homoserine Transacetylase: A Potential Antifungal Target”. İstanbul Journal of Pharmacy 51 (1): 137-40. https://izlik.org/JA38LU43RC.
EndNote
Seyran E (April 1, 2021) Fungal homoserine transacetylase: A potential antifungal target. İstanbul Journal of Pharmacy 51 1 137–140.
IEEE
[1]E. Seyran, “Fungal homoserine transacetylase: A potential antifungal target”, iujp, vol. 51, no. 1, pp. 137–140, Apr. 2021, [Online]. Available: https://izlik.org/JA38LU43RC
ISNAD
Seyran, Esra. “Fungal Homoserine Transacetylase: A Potential Antifungal Target”. İstanbul Journal of Pharmacy 51/1 (April 1, 2021): 137-140. https://izlik.org/JA38LU43RC.
JAMA
1.Seyran E. Fungal homoserine transacetylase: A potential antifungal target. iujp. 2021;51:137–140.
MLA
Seyran, Esra. “Fungal Homoserine Transacetylase: A Potential Antifungal Target”. İstanbul Journal of Pharmacy, vol. 51, no. 1, Apr. 2021, pp. 137-40, https://izlik.org/JA38LU43RC.
Vancouver
1.Esra Seyran. Fungal homoserine transacetylase: A potential antifungal target. iujp [Internet]. 2021 Apr. 1;51(1):137-40. Available from: https://izlik.org/JA38LU43RC