The effects of polymer phase ratio and feeding strategy on solid-liquid TPPBs for the production of L-phenylacetylcarbinol from benzaldehyde using Candida utilis.

To increase the bioproduction of L-phenylacetylcarbinol (PAC), a precursor molecule in the synthesis of the decongestants ephedrine and pseudoephedrine and which suffers from substrate, product, and by-product inhibition, by ensuring that the delivery of the substrate, benzaldehyde, is maintained within a strict concentration window. Beads of the commercial polymer, Hytrel G3548L, can act as a sequestering phase to reduce inhibitory effects to cells of Candida utilis while creating a reservoir for high concentrations of products. In this work we varied the polymer phase volume ratio (from 3 to 15%), and modified the benzaldehyde feeding strategy to further improve on system performance, resulting in greater than 100% increase in the PAC productivity relative to a single phase control, as well as robust operation of the two-phase bioreactor with minimal operator intervention.

Bioproduction of benzaldehyde in a solid-liquid two-phase partitioning bioreactor using Pichia pastoris.

The bioproduction of benzaldehyde from benzyl alcohol using Pichia pastoris was examined in a solid-liquid two-phase partitioning bioreactor (TPPB) to reduce substrate and product inhibition. Rational polymer selection identified Elvax 40W as an effective sequestering phase, possessing partition coefficients for benzyl alcohol and benzaldehyde of 3.5 and 35.

Application of solid-liquid TPPBs to the production of L-phenylacetylcarbinol from benzaldehyde using Candida utilis.

The biotransformation of benzaldehyde and glucose to L-phenylacetylcarbinol (PAC) using Candida utilis was demonstrated in a solid-liquid two-phase partitioning bioreactor (TPPB) with the aim of reducing substrate, product, and by-product toxicity via sequestration. Previous work in the field had used octanol as the sequestering phase of liquid-liquid TPPBs but was limited by the toxic effects of octanol on C. utilis.