Self-sufficient biocatalytic cascade for the continuous synthesis of danshensu in flow

A new strategy has been developed for the successful production of the active component danshensu ex vivo. For this purpose, phenylalanine dehydrogenase from Bacillus sphaericus was combined with a novel hydroxyphenylpyruvate reductase from Mentha x piperita, thereby enabling in situ cofactor regeneration throughout the conversion process. The enzymes were purified, co-immobilized, and subsequently employed in batch biotransformation, resulting in 60% conversion of 10 mM L-dopa within 24 hours, using a catalytic amount of NAD⁺ as cofactor. Furthermore, the bienzymatic system was implemented as a packed-bed reactor in continuous flow, with conversion rates of up to 80% being achieved at a retention time of 60 minutes. Process intensification was accomplished by conducting a 48-hour flow bioreaction. The biocatalysts demonstrated remarkable stability, with 62% of their initial activity retained at the conclusion of the process. The final productivity of the isolated compound, obtained at 96% purity, was calculated to be 1.84 g L⁻¹ h⁻¹, thereby yielding a sustainable synthesis of danshensu.

• Marchini, V
• Paradisi, F

• Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland

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