## 4 Discussion
In order to minimize deviations from the baseline PAs content, key biosynthetic enzymes such as ODC, SamDC and SpdS are tightly controlled at the levels of transcription, translation, and cell lifespan [32; 49]. In this regard, the shift in PAs cell content is accompanied with several mutational events, corresponding to changes in at different levels of the regulation. Previously, we found an increased content of PAs in _A. chrysogenum_ high-yielding producer of cephalospor Cor (CPC) [21]. This strain also showed increased resistance to ODC inhibitors [21]. Possibly, the concentration of 5 mM ODC inhibitors was sufficient for complete depletion of PAs pool in _A. chrysogenum_ WT strain and was insufficient to deplete the PAs pool in the _A. chrysogenum_ HY strain. In the current study, we showed for _A. terreus_ HY strain the increased resistance to DFMO and APA inhibitors of ODC, as well as _odc_ upregulation and _oaz_ downregulation. The shift in PAs content in filamentous fungi strains obtained as a result of CSI programs, has recently been proposed [16; 21]. As a result of multi-round random mutagenesis and screening, useful mutations are selected, leading to an increase in the yield of the target SM [16]. Along with this, a genetic load accumulates which represents side mutations and is expressed in a general decrease of strains fitness and a reduction in other vital processes [10; 17; 50]. In response to mutagenic effects, the cell activates its protective resources; PAs are also known to be able to protect cells from free radical damage through direct interaction with reactive oxygen species [51; 52]. Recently, it was shown that PAs can promote homologous recombination during DNA repair complexed with RAD51, stimulating the formation of RAD51-ssDNA nucleofilaments [53]. Thus, an increase in the PAs content could be a side effect during multi-round mutagenesis, which made it possible to obtain a viable strain after the next exposure [16; 21]. At the same time, the metabolism of PAs can intersect with SM biosynthesis at the level of consumption of common substrates, for example, SAMe [32]. The SAMe coenzyme is used both for transmethylation reactions during LOV biosynthesis and for aminoproylation during PAs biosynthesis (Figures 4 and 5). It is known that the biosynthesis of one LOV molecule requires two SAMe molecules [54]. For the synthesis of one molecule of Spd, one molecule of SAMe molecule is required; to synthesize one Spm molecule (from putrescine), two SAMe molecules are required [16]. The observed upregulation of genes for PAs biosynthesis (including _samdc_ gene, coding SAMe-consuming enzyme), amid upregulation of _lov_ genes (including _lovB_ and _lovF_ genes, coding SAMe-consuming enzymes), may lead to the depletion of the SAMe content during fermentation with 10-15 g/L yield of LOV (Figure 5). It has also been shown that SAMe is required for the functioning of epigenetic factors, SAMe-dependent methyl-transferases of DNA and histones, the most important of which is LaeA, a positive regulator of LOV biosynthesis in _A. terreus_[55] or beta-lactams in _Penicillium chrysogenum_[56; 19] and _A. chrysogenum_[20]. In this regard, maintaining an increased pool of PAs in improved strains partly takes up the resources required for the biosynthesis of the target SM. The introducing of exogenous PAs can lead by a feedback mechanism to a decrease in PAs endogenous biosynthesis [32] and the release of resources, for example, SAMe, for the production of the target SM. This may explain the additional increase in production in the improved strains during fermentation with PAs [16].