Advanced process design for large-scale de-novo 2-phenylethanol production via fermentation

Abstract

BACKGROUND: 2-Phenylethanol (2PE) is a valuable aroma component that can be obtained through de-novo fermentation from glucose. However, its toxicity at very low concentrations (<2.5 g L−1) limits the fermentation titer, rate and yield. To address these limitations, in-situ product removal has been explored, leading to a recent scale-up to pilot scale. Nonetheless, an industrial scale has yet to be achieved. RESULTS: This original research pioneers conceptual development of two large-scale (2 ktonne2PE/y) production processes for 2PE via de-novo fermentation from glucose. Liquid–liquid extraction with oleyl alcohol and adsorption by hydrophobic resins followed by ethanol desorption, were alternatives considered for in-situ 2PE removal. For either design, solvent recovery and final purification were performed using advanced distillation techniques, including a heat pump-assisted distillation and a dividing-wall column. A fermentation titer of approximately 1.5 g2PE/Lbroth minimized production costs by achieving balance between upstream and downstream processing costs. This resulted in a cost-effective 2PE production for both designs of the recovery process (9.03–9.40 $/kg2PE). Sensitivity analysis revealed that glucose, oleyl alcohol, and ethanol costs strongly impact total production costs. CONCLUSION: This novel study provides a comprehensive and scalable process framework for the large-scale production of 2PE through de-novo fermentation. Integrating in-situ product removal and energy-efficient purification strategies, it marks a significant step forward in industrial biotechnology. © 2025 The Author(s). Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).