Resveratrol production by grapevine cells in fed-batch bioreactor: Experiments and modelling

Abstract

The purpose of this work was to scale-up the culture of grapevine cells (Vitis labrusca) from shake-flasks (100 mL) to a 5L stirred bioreactor in order to study the bioproduction of resveratrol under controlled conditions. Biomass, resveratrol and sugar concentrations as well as pH and dissolved oxygen were monitored daily. The experiments were conducted twice for a total period of two months. The culture was elicited during the exponential growth phase with methyl jasmonate, leading the cells to exhibit a non-trivial behaviour during the resveratrol production phase. A model of the system behaviour involving simple phenomenology is proposed and validated against the experimental results. This model demonstrates that the system dynamic can be decomposed into four phases: a lag phase (cell growth slowing down), a starting phase (beginning of resveratrol production), a surge phase (significant resveratrol production, important cell death) and a stationary phase.

Optimize, Modulate, and Scale-up Resveratrol and Resveratrol Dimers Bioproduction in Vitis labrusca L. Cell Suspension from Flasks to 20 L Bioreactor

“…It is then of importance to determine how to maximize the production of the desired compounds with the lowest cell concentration possible and to maximize the concentration of stilbenes in an elicited cell suspension. We supposed that the MeJA elicitation effect depended on the cell concentration and the sucrose content at the time of elicitation, as suggested by previous studies [35][36][37]. A full factorial experimental design was used to evaluate the combined effects of biomass, MeJA, and sucrose concentrations at the time of elicitation on the stilbene concentration.…”

“…Vitis cells cultivated in vitro not only produce resveratrol and piceid, but a large diversity of compounds, from monomers like piceatannol, astringin, resveratroloside, resveratrol di-and triglucosides, to dimers such as pallidol, ε-viniferin, δ-viniferin, and leachianols F and G [4,20,[28][29][30][31][32][33], and a new dimer named labruscol was recently identified in V. labrusca cell suspension [5]. Biological activities of resveratrol oligomers are attracting the attention of scientists, but their level of production in grapevine cell culture is low: In the order of milligrams per liter (mg/L) or milligrams per kilogram (mg/kg) of fresh weight [31,34,35]. So it is of great interest to increase their production.…”

Synthesis and Characterization of Novel Resveratrol Butyrate Esters That Have the Ability to Prevent Fat Accumulation in a Liver Cell Culture Model

“…It has been found in over 70 types of plants, including grape skin, grape seeds, giant knotweed, peanut, cassia seed, passion fruit, white tea, plums, and peanuts. It has powerful antioxidant activity and plays a role in the defense against pathogen infection, injury, and abiotic stress [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. RE has been used in medicines, dietary supplements, and functional foods, and the excellent health benefits of RE have also been confirmed by several studies.…”

“…RE has been used in medicines, dietary supplements, and functional foods, and the excellent health benefits of RE have also been confirmed by several studies. It has preventive effects on oxidative stress, inflammation, and cardiovascular disease, and shows anti-carcinogenic activity [ 3 , 8 , 9 , 10 ]. Furthermore, RE has been proven to reduce the risk of developing diseases by inhibiting advanced glycation end product formation [ 11 ].…”

Green (cell) factories for advanced production of plant secondary metabolites

“…Fresh medium was added at 141 and 212 h respectively, while the elicitor (0.5 mM MeJa) was added when sucrose was completely depleted. The resveratrol concentration remained approximately zero during the first 7 days after elicitation and reached a maximum of 66 mg/L on day 12 [42]. After the optimization of the sucrose (30 g/L), inoculum (40 g/L) and chitosan (50 mg/L) concentrations in a batch process, a fed-batch process in 1-L stirred tank bioreactor for the cultivation of V. vinifera cv.…”