## 1 Introduction  
Filamentous fungus _Aspergillus terreus_ is the main industrial producer of cholesterol-lowering drug lovastatin (LOV) and simvastatin obtained on its basis [1]. These drugs are competitive inhibitors of hydroxymethylglutaryl-CoA reductase (HMG-CoA; EC 1.1.1.88), which catalyzes the rate-limiting step of the isoprenoid biosynthesis pathway associated with the production of cholesterol in humans and ergosterol in fungi [2]. In nature, LOV is produced by fungi from various taxonomic groups, for example, _Ascomycetes_, _Aspergillus_, _Doratomyces_, _Gymnoascus_, _Hypomyces_, _Monascus_, _Paeciolimyces_, _Penicillium_, _Phoma_, _Trichderm_ or basidiomycetes _Lenzites_, _Omphalotus_, _Phanerochaete_, _Pleurotus_, _Trametes_ and many others [3; 4; 5]. Since, in fungi, this secondary metabolite (SM) inhibits the biosynthesis of ergosterol, which is necessary for building the cytoplasmic membrane, the fungal LOV producers should be resistant themselves to it [6; 7]. This is realized by placing into the LOV biosynthetic gene cluster (BGC, _lov_ genes) not only genes for biosynthesis but also for LOV resistance [7; 8]. Since _lov_ genes for biosynthesis are linked to genes for LOV resistance, the horizontal transfer of _lov_ BGC to one or another representative of fungi kingdom gives them the ability to not only attack competitors with LOV weapons, but also to defend themselves from exogenous LOV [8]. This may explain such a wide distribution of _lov_ BGC in fungi [3]. The most important industrial LOV-producing strains are derived from _A. terreus_[1]. In the current study, we investigated _A. terreus_ lovastatin high-yielding (HY) strain obtained after classical strain improvement (CSI) program after multi-round mutagenesis and screening [9]. In _A. terreus_ HY strain, the LOV production is increased 200-300-fold compared to the original _A. terreus_ wild-type (WT) strain [9; 10]; _lov_ genes and _laeA_ gene (for global regulator of a fungal secondary metabolism) are upregulated [10; 11]; the number of _lov_ BGC copies does not increase [12]. The _A. terreus_ HY strain also demonstrates a significant decrease in viability, expressed in a decrease in the growth rate on agar and liquid nutrient media, a partial reduction in the formation of conidia and the size of mycelium [10; 12]. This may be due to the fact that CSI programs operate with random mutations and, during strain improvement, concomitant changes can be accumulated that negatively affect strain viability [13; 14; 15]. As a result, in the process of multi-round mutagenesis, a stage begins when the next mutagenic effect no longer leads to a further increase in the production of the target SM [16]. This final stage usually occurs after 20-50 rounds of mutagenesis, and determines the technological limit of the method, in relation to a particular strain [9; 16; 17; 18]. Previously, it was shown that exogenously introduced polyamines (PAs), such as 1,3-diaminopropane (DAP) or spermidine (Spd), are able to increase the production of target SM in strains that have reached their technological limit [19; 20]. In our previous work, we showed that the addition of PAs to complete agar medium leads to an increase in the viability of _A. terreus_ HY, which is expressed in an increase in the number of germinating colonies [12]. Furthermore, the addition of 5 mM Spd during the fermentation of _A. terreus_ HY increased the LOV yield by 20-45% and was accompanied by upregulation of the _lov_ genes and _laeA_; however, the molecular mechanisms involved in this process have not been studied [12]. Recently, _Acremonium chrysogenum_ cephalospororin C (CPC) high-yielding strain showed an increase in the content of PAs during the fermentation process, about 5-fold [21]. The improved strain _A. chrysogenum_ strain also demonstrated the increased resistance to inhibitors of ornithine decarboxylase (ODC; EC 4.1.1.17), an enzyme of the key stage of PAs biosynthesis [21].