## 3 Results  
### Inhibitory Analysis of A. terreus Cell Growth by DFMO and APA  
The analysis of ODC inhibition in _A. terreus_ WT and HY strains was carried out on CDA synthetic medium, which did not contain PAs. The inhibition was assessed quantitatively by comparing the colony growth. ODC is the first and rate-limiting enzyme of PAs _de novo_ synthesis in filamentous fungi; in this regard, inhibition of this enzyme on a synthetic medium without PAs can lead to a significant or complete loss of growth of fungal cells [16; 21]. Inhibitory analysis was performed using DFMO, an irreversible suicide inhibitor of ODC, recently studied _versus_ ODC from _A. terreus_[27], and APA, isosteric hydroxylamine-containing analogue of Put, showing more potent ODC inhibition than DFMO in some filamentous fungi [21; 28]. Aliquots of fungal cells were inoculated onto CDA medium supplemented with compounds or without them (control) (Figure 1).  
The inhibitors were added in the concentration range 0.1-5 mM. To determine the specificity of inhibition on PAs biosynthetic pathway by removing the effect of growth inhibition, CDA/DFMO media or CDA/APA media were also supplmented with 0.5 mM Spd. To evaluate the effect of inhibition and removal of inhibition with Spd, fungal strains were also cultured on CDA media without additives and with the addition of only 0.5 mM Spd. The cultivation was carried out for 21 days at 26 \({}^{\circ}\)C. The inhibitory effect was determined quantitatively as the percentage of colony growth inhibition on CDA medium with the additions compared to the control medium (Figure 2 and Table S1).  
Figure 1: Growth inhibition of the WT (wild type) and HY (high-yielding lovastatin producer) _A. terreus_ strains with 1 and 5 mM \(\alpha\)-difluororphinithine (DFMO), 1 and 5 mM 1-aminooxy-3-aminopropane (APA) and the reversal of the inhibition with 0.5 mM spermidine (Spd) at 15 days after inoculation on agarized Czapek-Dox (CDA) medium.  
The maximum growth inhibition was observed at the early stages of cultivation for both strains and with the addition of both inhibitors (Figure 2). Further, by the 18 th day, there was a gradual overcoming of the toxic effect, expressed in a decrease of growth inhibition. This happened in all cases, except for the effect of 5 mM APA on _A. terreus_ WT, leading to the complete death of this strain, 100% inhibition (Figures 1 and 2d). At the same time, _A. terreus_ HY exhibited increased resistance and showed growth on CDA medium with the addition of 5 mM APA (Figures 1 and 2d). Such increased resistance of the high-yielding LOV producer was shown against both studied ODC inhibitors (Figure 1). After 15 days of cultivation, _A. terreus_ HY was more resistant to 5 mM DFMO, by 20-25%, and to 5 mM APA, by 40-45% (Figures 1 and 2b,d). Removal of the toxic effect of inhibitors when Spd was added together was approximately the same for both strains. The addition of Spd, together with DFMO or APA, led not only to the recovery (or partial recovery) of colony size, but also to the recovery of initial strain phenotype, colony color and morphology, for both strains (Figure 1). The lethal effect of 5 mM APA for the _A. terreus_ WT strain was removed by supplementation of 0.5 mM Spd; the _A. terreus_ WT strain growth on CDA/5 mM APA/0.5 mM Spd media after 15 days was approximately 50% of the control (Figures 1 and 2d).  
Figure 2: Growth inhibition of the _A. terreus_ WT and HY strains with 1 and 5 mM DFMO, 1 and 5 mM APA and the reversal of the inhibition with 0.5 mM Spd on CDA medium. Growth inhibition (%) of _A. terreus_ WT and HY strains with 1 mM DFMO (**a**), 5 mM DFMO (**b**), 1 mM APA (**c**), 5 mM APA (**d**), and reverse of the inhibition with 0.5 mM Spd (**a–d**). Data are means \(\pm\) SD, \(n=3\). ND, not detected.