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Open AccessArticle

High-Yielding Lovastatin Producer Aspergillus terreus Shows Increased Resistance to Inhibitors of Polyamine Biosynthesis

1
Research Center of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia
2
Moscow Institute of Physics and Technology, National Research University, 141700 Dolgoprudny, Russia
*
Author to whom correspondence should be addressed.
Appl. Sci. 2020, 10(22), 8290; https://doi.org/10.3390/app10228290
Received: 20 October 2020 / Revised: 13 November 2020 / Accepted: 20 November 2020 / Published: 23 November 2020
(This article belongs to the Section Applied Biosciences and Bioengineering)
The biosynthesis of pharmaceutically significant secondary metabolites in filamentous fungi is a multistep process that depends on a wide range of various factors, one of which is the intracellular content of polyamines. We have previously shown that in Aspergillus terreus lovastatin high-yielding strain (HY) exogenous introduction of polyamines during fermentation can lead to an increase in the production of lovastatin by 20–45%. However, the molecular mechanisms of this phenomenon have not been elucidated. In this regard, we carried out an inhibitory analysis at the key stage of polyamine biosynthesis, the conversion of L-ornithine to putrescine by the enzyme ornithine decarboxylase (ODC). A. terreus HY strain showed upregulation of genes for biosynthesis of polyamines, 3–10-fold, and increased resistance compared to the original wild-type strain upon inhibition of ODC on synthetic medium with 5 mM α-difluoromethylornithine (DFMO), by 20–25%, and 5 mM 1-aminooxy-3-aminopropane (APA), by 40–45%. The data obtained indicate changes in the metabolism of polyamines in A. terreus HY strain. The observed phenomenon may have a universal character among fungal producers of secondary metabolites improved by classical methods, since previously the increased resistance to ODC inhibitors was also shown for Acremonium chrysogenum, a high-yielding producer of cephalosporin C. View Full-Text
Keywords: polyamines; Aspergillus terreus; ornithine decarboxylase; filamentous fungi; secondary metabolism polyamines; Aspergillus terreus; ornithine decarboxylase; filamentous fungi; secondary metabolism
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MDPI and ACS Style

Zhgun, A.A.; Nuraeva, G.K.; Volkov, I.A. High-Yielding Lovastatin Producer Aspergillus terreus Shows Increased Resistance to Inhibitors of Polyamine Biosynthesis. Appl. Sci. 2020, 10, 8290. https://doi.org/10.3390/app10228290

AMA Style

Zhgun AA, Nuraeva GK, Volkov IA. High-Yielding Lovastatin Producer Aspergillus terreus Shows Increased Resistance to Inhibitors of Polyamine Biosynthesis. Applied Sciences. 2020; 10(22):8290. https://doi.org/10.3390/app10228290

Chicago/Turabian Style

Zhgun, Alexander A.; Nuraeva, Gulgina K.; Volkov, Ivan A. 2020. "High-Yielding Lovastatin Producer Aspergillus terreus Shows Increased Resistance to Inhibitors of Polyamine Biosynthesis" Appl. Sci. 10, no. 22: 8290. https://doi.org/10.3390/app10228290

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