A Stilbenoid-Specific Prenyltransferase Utilizes Dimethylallyl Pyrophosphate from the Plastidic Terpenoid Pathway

Abstract

Prenylated stilbenoids synthesized in some legumes exhibit plant pathogen defense properties and pharmacological activities with potential benefits to human health. Despite their importance, the biosynthetic pathways of these compounds remain to be elucidated. Peanut (Arachis hypogaea) hairy root cultures produce a diverse array of prenylated stilbenoids upon treatment with elicitors. Using metabolic inhibitors of the plastidic and cytosolic isoprenoid biosynthetic pathways, we demonstrated that the prenyl moiety on the prenylated stilbenoids derives from a plastidic pathway. We further characterized, to our knowledge for the first time, a membrane-bound stilbenoid-specific prenyltransferase activity from the microsomal fraction of peanut hairy roots. This microsomal fraction-derived resveratrol 4-dimethylallyl transferase utilizes 3,3-dimethylallyl pyrophosphate as a prenyl donor and prenylates resveratrol to form arachidin-2. It also prenylates pinosylvin to chiricanine A and piceatannol to arachidin-5, a prenylated stilbenoid identified, to our knowledge, for the first time in this study. This prenyltransferase exhibits strict substrate specificity for stilbenoids and does not prenylate flavanone, flavone, or isoflavone backbones, even though it shares several common features with flavonoid-specific prenyltransferases.

Gnetin‐C and other resveratrol oligomers with cancer chemopreventive potential

“…In nature, resveratrol is produced by certain plants in response to stress stimuli, such as microbe infection, injury, and ultraviolet radiation . After its biosynthesis, resveratrol can undergo structural modifications, such as glycosylation, prenylation, geranylation, and oligomerization . Resveratrol oligomers are formed by the polymerization of two or more resveratrol units to generate dimers, trimers, tetramers, and even more complex derivatives.…”

Stilbenoids: A Natural Arsenal against Bacterial Pathogens

“…In 2020, in order to perform SAR studies, Catinella et al [115] synthesised a series of simplified derivatives of dehydro-δ-viniferin and viniferifuran by a systematic removal of the moieties linked to the benzofuran ring and evaluated the antibacterial activity against the foodborne pathogen Listeria monocytogenes Scott A (Figure 20). The simplified derivatives of dehydro-δ-viniferin (63)(64)(65) demonstrated a significant loss of the antibacterial efficacy compared to the parent compound, suggesting in this case the importance of all three phenolic rings linked to the benzofuran core for the activity. Conversely, the structural simplification of viniferifuran (MIC = 16 µg/mL, MBC > 512 µg/mL) led to compound 67 with improved activity (MIC = 8 µg/mL; MBC = 64 µg/mL) against L. monocytogenes, which is comparable to the standard chlorhexidine.…”

“…Prenylated stilbenoids are mainly isolated from the Leguminosae family, e.g., soybean, peanuts, mung bean, and their production can be stimulated by fungal elicitation. In particular, a prenyltransferase is responsible for attaching a prenyl-moiety to the phenol ring, and in the case of peanut stilbenoids, the prenylation usually occurs at the para position [63]. The prenyl-chain (3,3-dimethylallyl or 3-methyl-but-1-enyl substituent) may undergo further enzymatic cyclisation with an ortho-phenolic hydroxy group leading to five-or six-membered rings, which are furan and pyran derivatives respectively [64].…”

Dietary Pterostilbene and Resveratrol Modulate the Gut Microbiota Influenced by Circadian Rhythm Dysregulation

“…The original function of these phenolic compounds derived from phenylpropanoid pathway is phytoalexins that provide plants defensive effect against pathogens. [ 16,17 ] Stilbenoids gained their attention exhibiting several anti‐cancer and anti‐tumor effects, ameliorative effect on inflammatory and metabolic related diseases and other biological and pharmacological benefits. [ 18,19 ] Among them, resveratrol (RES) ( trans ‐3,5,4’‐trihydroxystilbene) and its dimethylated counterpart, pterostilbene (PSB) (trans‐3,5‐dimehoxy‐4’‐hydroxystilbene) have been widely studied.…”