*Biosynthesis and Nutraceutical Availability*

The biosynthesis of PTS is facilitated through the conversion of the amino acids phenylalanine or tyrosine, which are products of the shikimate pathway. These amino acids are converted to coumarate and then to p-coumaroyl-CoA, resulting in the production of precursor stilbenes. While stilbene synthase converts precursor stilbenes to resveratrol, an O-methyl transferase further methylates two of the resveratrol hydroxyl groups of resveratrol to form PTS [15].

The availability of PTS in plants was found to vary within species based on various genetic and environmental factors [16]. Interestingly, fungal infection induced the elevated production of PTS in certain food crops, such as grapes [17]. Further, exposure to ultraviolet light amplified the production of resveratrol, while it reduced the production of PTS in grapevines [18]. The concentration of PTS was observed to be relatively high in the fruit skins or epidermal tissues of plants. This could be an evolutionarily conserved effect to protect the plant from harmful microbes that could cause infection through the penetration of the plant epidermis [19]. The variability in the nutraceutical availability within a single plant indicates that different conditions are required to produce resveratrol and PTS. The transgenic alteration of phenolic metabolism has been proposed as a key strategy to improve the yield of PTS from dietary sources. Notably, PTS was produced even by species that do not produce the compound through transgenic alteration. Tobacco (*Nicotiana tabacum* L.) and *Arabidopsis thaliana* (L.) Heynh. were transformed to produce PTS by employing a stilbene synthase transgene from peanut along with an O-methyltransferase transgene from *Sorghum* bicolor (L.) Moench [10]. Of note, the production of PTS in tobacco was accompanied by reduced flavonoid levels, indicating that stilbenes and flavonoids compete for p-coumaroyl-CoA in their biosynthesis pathways.

Additionally, PTS production has been reported to be amplified in food crops that already produce the compound through metabolic engineering. In grapevine cell cultures that were transformed to constitutively express *V. vinifera* O-methyltransferase, PTS production was observed to be elevated [20]. An effort was also made to employ stilbenesynthesizing gut bacteria to provide a constant PTS supply to animals without the dietary ingestion of the compound [21].

#### **3. Analytical Aspects**

Stilbenoids are a class of non-flavonoid polyphenolic compounds with a molecular weight of approximately ∼200–300 g/mol [22]. Some of the members of the stilbene family include resveratrol, PTS, and 3 -hydroxy PTS [22]. Stilbenoids are characterized by a C6-C2-C6 skeleton and the presence of phenyl groups that are linked by ethene double bonds [22]. With a molecular weight of 256.29 g/mol, PTS is a 3,5-dimethoxy analog of resveratrol [22]. PTS is a methoxybenzene and a diether due to the presence of transstilbene with methoxy groups at the 3 and 5 positions and a hydroxy group at the 4 position [22]. Even though PTS exists in both cis and trans structures, it is most abundant in its monomeric, lipid-soluble trans form [9]. Upon the equimolar administration of resveratrol and PTS in rats, systemic exposure and the plasma concentration (higher Cmax and AUC0–inf) were greater in PTS when compared to resveratrol, whereas the total body clearance of resveratrol was greater than that of PTS [4]. The two methoxy groups in PTS have been identified as responsible for increasing its oral absorption and bioavailability compared to resveratrol [22].
