High-Yielding Lovastatin Producer Aspergillus terreus Shows Increased Resistance to Inhibitors of Polyamine Biosynthesis
Research Center of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia
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.