Pré-Publication, Document De Travail Année : 2026

Real-time fermentation tracking of p-coumaric acid using Waveguide-Enhanced Raman Spectroscopy (WERS)

Résumé

The efficient bioproduction of p-coumaric acid (p-CA) in Saccharomyces cerevisiae remains limited by the compound's low solubility and inhibitory effects at elevated concentrations, highlighting the need for real-time process monitoring to support advanced control strategies. This study evaluates the use of waveguide-enhanced Raman spectroscopy (WERS) as an in situ, real-time analytical tool for tracking p-CA fermentation dynamics. A recently developed Raman-on-a-chip sensor successfully quantified key metabolites directly within turbid, complex fermentation media. Chemometric models built from Raman spectra accurately predicted p-CA, ethanol, glycerol, glucose and acetic acid concentrations, with Root Mean Squared Error of Prediction of 0.37 g.L -1 , 2.9 g.L -1 , 1.3 g.L -1 , 6.3 g.L -1 and 0.54 g.L -1 , and corresponding correlation coefficients of 0.63, 0.86, 0.80, 0.43 and 0.87. These performances support reliable monitoring and early detection of metabolic shift. When combined with an optimized semi-defined medium and fed-batch strategy, WERS provided a reproducible monitoring framework that supported improved p-CA production performance, representing a 2.3-fold increase compared to the batch process. Beyond demonstrating analytical feasibility, these results position WERS as a scalable Process Analytical Technology (PAT) suitable for integration into feedback-controlled or continuous extraction systems aimed at mitigating p-CA product inhibition to enhance yield, maintain culture viability, and streamline industrial p-CA biomanufacturing.

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Dates et versions

hal-05440085 , version 1 (04-01-2026)

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Identifiants

  • HAL Id : hal-05440085 , version 1

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Lieutaud Christopher, Perez Florent, Ompala Chardel, Emidio Rita, Godon Blandine, et al.. Real-time fermentation tracking of p-coumaric acid using Waveguide-Enhanced Raman Spectroscopy (WERS). 2026. ⟨hal-05440085⟩

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