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.
Microbes constitute important platforms for the biosynthesis of numerous molecules of pharmaceutical interest such as antitumor, anticancer, antiviral, antihypertensive, antiparasitic, antioxidant, immunological agents, and antibiotics as well as hormones, belonging to various chemical families, for instance, terpenoids, alkaloids, polyphenols, polyketides, amines, and proteins. Engineering microbial factories offers rich opportunities for the production of natural products that are too complex for cost-effective chemical synthesis and whose extraction from their originating plants needs the use of many solvents. Recent progresses that have been made since the millennium beginning with metabolic engineering of microorganisms for the biosynthesis of natural products of pharmaceutical significance will be reviewed.
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