## 2 Materials and Methods  
### Grapes from Vranec and Cabernet Sauvignon Variety for Winemaking and Chemicals  
Grapes were provided by local farmers from the Kavadarci wine-growing region (Kavadarci, North Macedonia). Grapes from Vranec (Tikves, Kavadarci, North Macedonia) and Cabernet Sauvignon (Tikves, Kavadarci, North Macedonia) varieties for this study were harvested in September 2016 and 2017 in the area of \"Crveni Bregovic\", located in the \"Tikves\" wine-growing region (Kavadarci North Macedonia). The grapes were harvested at their optimum time of maturation. Samples of undamaged grapes were taken at random for further analyses, placed in sterile bags (ISOLAB, Eschau, Germany) and kept in a refrigerator (Beko, Istanbul, Turkey) at 5 \({}^{\circ}\)C. All grape samples were stored for five days. Prior to the analyses, the grapes were selected manually by tossing out rotten or peculiar-looking grapes. After washing and removing the steams, the grapes were crushed to release the must. The total sugar content was determined according to the methodology described by the International Standard Method OIV-AS2-02-SUCREF (2007) [15], while titratable acidity and pH were determined by the International Standard Method OIV-AS-313-01-ACITOT (2009) [16]. These assays in grapes were performed in two replicates for each harvested year (two replicates for 2016 and two replicates for 2017) and the chemical parameters were determined in duplicate. All chemicals for these grape analyses were purchased from Sigma-Aldrich (Seelze, Germany) and Merck (Darmstadt, Germany), and were of analytical reagent grade. Isolation, Selection, and Identification of Autochthonous Yeast Strains F-8 and F-78 from the Tikves Wine-Growing Region  
The procedure of isolation and selection of endogenous yeast strains F-8 and F-78 was previously described by the research group of [PERSON] (2016, 2017, 2019) [17; 18; 19]. Briefly, spontaneous fermentations of 10 different lots Vranec and five different lots of Cabernet Sauvignon from different micro-regions were held. After destemming, crushing, and addition of sulfuric acid (dosage 20 mg/kg, 5% sulfuric acid), the spontaneous fermentation took place at 25-28 \({}^{\circ}\)C in polyethylene terephthalate (PET) vessels (Ilsen GmbH, Hovelhof, Germany). From the experimental trials, pure yeast cultures were isolated according to the [PERSON] method ([PERSON] et al., 2000) [20]. The microbial isolation was executed from single colonies, cultivated in test tubes with nutrient agar (NA) culture medium with sterilized grape juice in a thermostat in water bath at 25 \({}^{\circ}\)C. Subsequently, the isolated and purified strains were subjected to a three-stage selection based on their fermentation ability. Moreover, the fermentation activity of the selected pure yeast strains F-8 and F-78 was evaluated in sterilized liquid grape juice. In sterilized sample tubes with 10 mL of the aforementioned juice each yeast culture was inoculated, previously activated during 72-h using a sterile inoculating loop. The assays were carried out in a thermostatic water bath at 25 \({}^{\circ}\)C, and the evolution of the alcoholic fermentation was checked with a refractometer ([PERSON], Hamburg, Germany). The F-8 and F-78 autochthonous yeast strains were selected based on their superior technological characteristics. Afterward, 2 mL of liquid inoculums were inoculated in the prepared sterile tap glass bottles (0.5 L) for the evaluation of their fermentation activity. The bottles were closed with fermentation caps and the course of the fermentation was monitored by the evaluation of the levels of residual sugar. The first determination of sugar fermentation capacity of the selected yeasts was determined in Petri dishes by pouring each strain in a mixture of 0.6% (\(w/v\)) yeast extract solution with the addition of 0.2% (\(w/v\)) of each of the following carbohydrates: glucose, fructose, galactose, maltose, saccharose, and raffinose (in this last case, in a concentration of 0.4%, \(w/v\)).