Development of a Tailored Culture Medium for Improved De Novo Biosynthesis of Ferulic Acid in Fed-Batch Biphasic Fermentation with Saccharomyces cerevisiae

Ferulic acid (FA) is a natural phenolic compound with diverse biological properties, widely used in the food and cosmetic industries. Its production from fermentation is a promising strategy because its extraction from biomass is costly. To enable cost-effective microbial production, medium optimization is mandatory. In this study, we focused on applying a fed-batch biphasic strategy for the production of ferulic acid (FA) from d-glucose. FA production was first assessed in a classically defined medium, 2X Yeast Nitrogen Base (YNB) without amino acids, and complex Yeast Peptone Dextrose (YEPD) medium. Finally, as FA has deleterious antimicrobial properties, continuous extraction from the broth using fed-batch biphasic fermentation was implemented. Our results showed that YEPD medium resulted in the production of 207 mg·L−1 of FA in a medium composed of 30 g·L−1 d-glucose, 10 g·L−1 yeast extract, 1 g·L−1 (NH4)2SO4, 10 g·L−1 peptone, 4 g·L−1 KH2PO4 and 2 g·L−1 K2HPO4. Fed-batch biphasic fermentation system resulted in almost a two-fold increase in FA production compared to batch one (312.6 mg·L−1 and 176.7 mg·L−1, respectively) showing the importance of fed-batch biphasic fermentation and medium detoxification.