Abstract <p>A new strategy has been developed to successfully produce the active component danshensu ex vivo. For this purpose, phenylalanine dehydrogenase from <i>Bacillus sphaericus</i> was combined with the novel hydroxyphenylpyruvate reductase from <i>Mentha x piperita</i>, thereby providing an in situ cofactor regeneration throughout the conversion process. The purified enzymes were co-immobilized and subsequently employed in batch biotransformation, resulting in 60% conversion of 10&#xa0;mM L-dopa within 24&#xa0;h, with a catalytic amount of NAD⁺ as cofactor. Furthermore, the bienzymatic system was implemented as a packed-bed reactor in continuous flow, achieving a conversion rate up to 80% with 60&#xa0;min retention time. The process was further intensified by implementing a 48-h flow bioreaction. The biocatalysts demonstrated remarkable stability, retaining 62% of their initial activity at the end of the process. The final productivity of the isolated compound (96% purity) was calculated to be 1.84&#xa0;g L⁻¹&#xa0;h⁻¹ yielding a sustainable synthesis of danshensu.</p> Key points <p><i>• Characterization of the hydroxyphenylpyruvate reductase from Mentha x piperita</i></p> <p><i>• Bi-enzymatic system in a cascade reaction to produce danshensu</i></p> <p><i>• Purification and isolation</i><i> of the active compound danshensu</i></p> Graphical Abstract <p></p>