## 4 Discussion  
In our experiments, we found an increase in the resistance of _A. terreus_ HY strain to inhibitors of ODC, a key enzyme of PAs biosynthesis (Figure 2). It is known that in the cells of various organisms a strict control of homeostasis for PAs content take place [32]. For this, there are both pathways of biosynthesis and catabolism of PAs, which have been studied, to a large extent, in mammals and a number of model organisms [33; 34; 35]. In filamentous fungi, some stages of PAs metabolism and its regulation are still not fully understood [36]. Previously, there was a misconception that filamentous fungi lack spermine [37]. Then, for numerous representatives of filamentous fungi, the presence of spermine was shown [38; 39]. Our recent work on studying the composition of PAs in _A. chrysogenum_ the presence of spermine as one of the main components of the PAs pool was also shown [21]. On the other hand, the pathways of putrescine biosynthesis have not yet been finally established in filamentous fungi [40]. In bacteria and higher plants, this diamine can be synthesized either directly from L-ornithine by the ODC enzyme, or through several successive steps, which are preceded by decarboxylation of L-arginine by the arginine decarboxylase enzyme (ADC; EC 4.1.19). From the other side, mammals  
Figure 4: The putative pathway of polyamine (PAs) biosynthesis in _A. terreus_ and growth inhibition (%) of WT (wild type) and HY (high-yielding lovastatin producer) strains by 5 mM inhibitors of ornithine decarboxylase (ODC). Fifteen days after inoculation on CDA medium. Green and up arrow next to the protein name means upregulation of corresponding gene in _A. terreus_ HY strain; white and down arrow next to the protein name means downregulation of corresponding gene in _A. terreus_ HY strain. SAMe—S-adenosylmethionine; dcSAME—decarboxylated S-adenosylmethionine. OAZ—ornithine decarboxylase antizyme, AdoMetS—S-adenosylmethionine synthetase, SamDC—S-adenosylmethionine decarboxylase, SpdS—spermidine synthase, SpmS—spermine synthase, DFMO—\(\alpha\)-difluoromethylmithine, APA—1-aminooxy-3-aminopropane. have only an ODC-dependent pathway for putrescine biosynthesis. In a number of fungi, DFMO, a suicidal inhibitor of ODC, completely suppresses cell growth [41; 42]. At the same time, there are studies demonstrating increased sensitivity for some fungi to DFMA (\(\alpha\)-difluoromethylarginine), a suicidal ADC inhibitor [43; 44]. Since the ADC enzyme has not yet been found in fungi, it is assumed that the DFMA inhibition effect may result from the conversion of this compound to DFMO by the enzyme arginase (EC 3.5.3.1) [40; 45]. In a recent work, the enzymatic properties of ODC from _A. terreus_ were described [27]. It was shown that this enzyme, in addition to catalytic activity against L-ornithine, has residual catalytic activity against L-arginine [27]. In current work, the addition of 5 mM APA led to 100% inhibition of the growth of the WT strain (Figures 1 and 4). In addition, arginine-decarboxylating activity has been shown for fungi of the genus _Aspergillus_, leading to the formation of agmatine [46]. Therefore, 100% inhibition of _A. terreus_ WT cell growth by 5 mM APA means that in _A. terreus_ only ODC-dependent putrescine biosynthesis is functioning, or 5 mM APA nonspecifically inhibits fungal ADC, as demonstrated for high concentrations of APA versus ADC from _E. coli_[21]. From the other side, _A. terreus_ HY strain exhibited increased resistance to ODC inhibitors (Figure 2). In particular, when 5 mM APA completely suppressed the growth of _A. terreus_ WT strain, the growth inhibition of _A. terreus_ HY was only 62%; when 5 mM DFMO inhibited _A. terreus_ WT by 49%, inhibition of _A. terreus_ HY was 25% (Figure 4). The disruption of PAs regulation may trigger a number of pathological processes, leading, for example, to the depletion of the pool of S-adenosylmethionine (SAMe) used for the biosynthesis of PAs (Figure 4) [47; 48].