Developmentof a Tailored Culture Medium for Improved De Novo Biosynthesis of Ferulic Acid inFed-Batch Biphasic Fermentation with Saccharomyces cerevisiae

Abstract

Ferulicacid (FA) is a natural phenolic compound with diverse biological properties,widely used in the food and cosmetic industries. Its production fromfermentation is a promising strategy because its extraction from biomass iscostly. To enable cost-effective microbial production, medium optimization ismandatory. In this study, we focused on applying a fed-batch biphasicstrategy for the production of ferulicacid (FA) from d-glucose.FA production was first assessed in a classically defined medium, 2X YeastNitrogen 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 wasimplemented. Our results showed that YEPD medium resulted in the production of207 mg·L^-1 of FA in a medium composed of 30 g·L^-1 d-glucose, 10 g·L^-1 yeastextract, 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 resultedin 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-batchbiphasic fermentation and medium detoxification.

Keywords

Ferulicacid / Mediumoptimization / Saccharomyces cerevisiae / Biphasic fermentation / Design of experiments

Acknowledgments

The authors gratefully acknowledge Arnaud Haudrechy for proofreading the article.

Author Contributions

B.G.: Formal analysis, Investigation, Data curation; J.C.: Formal analysis, investigation; F.B. (Fanny Brunissen) & F.B. (Fanny Brunois): HPLC data acquisition and analysis; C.F.: Investigation; F.A.: Conceptualization, Project administration, Funding acquisition, Review and Editing; M.L.: Supervision. N.I.: Conceptualization, Methodology, Supervision, Formal analysis, Investigation, Writing—original draft, Writing—review & editing.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data will be made available on request.

Funding

This work was supported by the Région Grand Est (France), Conseil Départemental de la Marne (France), and Grand Reims (France). The Agence Nationale de la Recherche (ANR, Grant ANR-17-CE07-0046) funded strain construction.

Declaration of Competing Interest

The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported here.

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