Abstract
Ergosterol, a unique component of fungal cells, is not only important for fungal growth and stress responses but also holds great economic value. Limited studies have been performed on ergosterol biosynthesis in Aspergillus oryzae, a safe filamentous fungus that has been used for the manufacture of oriental fermented foods. This study revealed that the ergosterol biosynthesis pathway is conserved between Saccharomyces cerevisiae and A. oryzae 3.042 by treatment with ergosterol biosynthesis inhibitors and bioinformatics analysis. However, the ergosterol biosynthesis pathway in A. oryzae 3.042 is more complicated than that in S. cerevisiae as there are multiple paralogs encoding the same biosynthetic enzymes. Using RNA-seq, this study identified 138 and 104 differentially expressed genes (DEG) in response to the ergosterol biosynthesis inhibitors tebuconazole and terbinafine, respectively. The results showed that the most common DEGs were transport- and metabolism-related genes. There were only 17 DEGs regulated by both tebuconazole and terbinafine treatments and there were 256 DEGs between tebuconazole and terbinafine treatments. These results provide new information on A. oryzae ergosterol biosynthesis and regulation mechanisms, which may lay the foundation for genetic modification of the ergosterol biosynthesis pathway in A. oryzae.
Similar content being viewed by others
References
Wollam J, Antebi A (2011) Sterol regulation of metabolism, homeostasis and development. Annu Rev Biochem 80:885–916
Prasad R, Shah AH, Antifungals RMK (2016) Mechanism of action and drug resistance. Adv Exp Med Biol 892:327–349
Beni A, Soki E, Lajtha K, Fekete I (2014) An optimized HPLC method for soil fungal biomass determination and its application to a detritus manipulation study. J Microbiol Methods 103(4):124–130
Kodedova M, Sychrova H (2015) Changes in the sterol composition of the plasma membrane affect membrane potential, salt tolerance and the activity of multidrug resistance pumps in Saccharomyces cerevisiae. PLoS One 10(9):e0139306
Görög S (2011) Advances in the analysis of steroid hormone drugs in pharmaceuticals and environmental samples (2004–2010). J Pharm Biomed Anal 55(4):728–743
Whiteman MK, Jeng G, Samarina A, Akatova N, Martirosyan M, Kissin DM, Curtis KM, Marchbanks PA, Hillis SD, Mandel MG, Jamieson DJ (Jan 2016) Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness. Contraception 93(1):17–24
Hu Z, He B, Ma L, Sun Y, Niu Y, Zeng B (2017) Recent advances in ergosterol biosynthesis and regulation mechanisms in Saccharomyces cerevisiae
Hayakawa H, Sobue F, Motoyama K, Yoshimura T, Hemmi H (2017) Identification of enzymes involved in the mevalonate pathway of Flavobacterium johnsoniae. Biochem Biophys Res Commun 487(3):702–708
Klug L, Daum G (2014) Yeast lipid metabolism at a glance. FEMS Yeast Res 14(3):369–388
Lee SH, Raboune S, Walker JM, Bradshaw HB (2010) Distribution of endogenous farnesyl pyrophosphate and four species of lysophosphatidic acid in rodent brain. Int J Mol Sci 11(10):3965–3976
Ahmad A, Khan A, Manzoor N, Khan LA (2010) Evolution of ergosterol biosynthesis inhibitors as fungicidal against Candida. Microb Pathog 48(1):35–41
Müller C, Staudacher V, Krauss J, Giera M, Bracher F (2013) A convenient cellular assay for the identification of the molecular target of ergosterol biosynthesis inhibitors and quantification of their effects on total ergosterol biosynthesis. Steroids 78(5):483–493
Kristan K, Rizner TL (Mar 2012) Steroid-transforming enzymes in fungi. J Steroid Biochem Mol Biol 129(1–2):79–91
Mercer EI (1993) Inhibitors of sterol biosynthesis and their applications. Prog Lipid Res 32(4):357–416
Ryder NS (2010) Terbinafine: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol 126(s39):2–7
Goldstein AS, Frye LL (1996) Synthesis and bioevaluation of delta 7-5-desaturase inhibitors, an enzyme late in the biosynthesis of the fungal sterol ergosterol. J Med Chem 39(26):5092–5099
Machida M, Asai K, Sano M, Tanaka T, Kumagai T, Terai G, Kusumoto KI, Arima T, Akita O, Kashiwagi Y, Abe K, Gomi K, Horiuchi H, Kitamoto K, Kobayashi T, Takeuchi M, Denning DW, Galagan JE, Nierman WC, Yu J, Archer DB, Bennett JW, Bhatnagar D, Cleveland TE, Fedorova ND, Gotoh O, Horikawa H, Hosoyama A, Ichinomiya M, Igarashi R, Iwashita K, Juvvadi PR, Kato M, Kato Y, Kin T, Kokubun A, Maeda H, Maeyama N, Maruyama JI, Nagasaki H, Nakajima T, Oda K, Okada K, Paulsen I, Sakamoto K, Sawano T, Takahashi M, Takase K, Terabayashi Y, Wortman JR, Yamada O, Yamagata Y, Anazawa H, Hata Y, Koide Y, Komori T, Koyama Y, Minetoki T, Suharnan S, Tanaka A, Isono K, Kuhara S, Ogasawara N, Kikuchi H (2005) Genome sequencing and analysis of Aspergillus oryzae. Nature 438(7071):1157–1161
Zhao G, Yao Y, Chen W, Comparison CX (2013) Analysis of the genomes of two Aspergillus oryzae strains. J Agric Food Chem 61(32):7805–7809
Bhattacharya S, Esquivel BD, White TC (2018) Overexpression or deletion of ergosterol biosynthesis genes alters doubling time, response to stress agents and drug susceptibility in Saccharomyces cerevisiae, mBio 9(4):e01291–18
Long M, Li ZQ, Lei B et al (2016) Identification and comparative study of chemosensory genes related to host selection by legs transcriptome analysis in the tea geometrid Ectropis obliqua. PLoS One 11(3):e0149591
Audic S, Claverie JM (1997) The significance of digital gene expression profiles. Genome Res 7(10):986–995
Blanc G, Gallot-Lavallée L, Maumus F (2015) Provirophages in the Bigelowiella genome bear testimony to past encounters with giant viruses. Proc Natl Acad Sci U S A 112(38):5318–5326
Wriessnegger T, Pichler H (2013) Yeast metabolic engineering – targeting sterol metabolism and terpenoid formation. Prog Lipid Res 52(3):277–293
Mikeš V, Lochman J, Kašparovský T (2006) Ergosterol is a signal molecule that leads to the expression of defence-related genes in tobacco
Acknowledgments
This study was financially supported by the National Natural Science Foundation of China (NSFC) (Grant nos. 31700068 and 31460447), International S&T Cooperation Project of Jiangxi Provincial (Grant no. 20142BDH80003), General Science and Technology Project of Nanchang City (Grant no. 3000035402), “555 Talent Project” of Jiangxi Province, Natural Science Foundation of Jiangxi Province (Grant nos. 20181BAB214001 and 20171BAB214004), and the Open Foundation of Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization (Grant no. EWPL201705).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Responsible Editor: Rosana Puccia
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hu, Z., Li, G., Sun, Y. et al. Gene transcription profiling of Aspergillus oryzae 3.042 treated with ergosterol biosynthesis inhibitors. Braz J Microbiol 50, 43–52 (2019). https://doi.org/10.1007/s42770-018-0026-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42770-018-0026-1