Journal
APPLIED SCIENCES-BASEL
Volume 10, Issue 22, Pages -Publisher
MDPI
DOI: 10.3390/app10228290
Keywords
polyamines; Aspergillus terreus; ornithine decarboxylase; filamentous fungi; secondary metabolism
Categories
Funding
- Russian Foundation for Basic Research [19-04-01173]
- Ministry of Science and Higher Education of the Russian Federation [075-00337-20-03, FSMG-2020-0007]
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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 alpha-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.
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