Production of 4-valerolactone by an equilibrium-limited transformation in a partitioning bioreactor: impact of absorptive polymer properties

Abstract

The biotransformation of levulinic acid to 4-valerolactone (4VL) is pH-dependent and equilibrium limited, distinct from the more common irreversible biotransformations that are constrained by product toxicity or biocatalyst inhibition. Our processing strategy for this system was to selectively remove the product, 4VL, which is in equilibrium with its precursor, 4-hydroxyvalerate (4HV), to pull the reaction to a greater extent of conversion. 4VL is challenging to separate from the aqueous phase due to its water miscibility, necessitating the use of water-absorbing polymers to provide affinity toward the hydrophilic product. Manipulating the composition of copolymers, thereby varying the architecture of polymer chains, conferred drastically different extents of water absorption and caused different biotransformation outcomes. A custom-synthesized random copolymer designed to maximize the proportion of material with affinity for the solute had high water uptake, which resulted in the poor selectivity for the target molecule relative to its precursor. Conversely, a moderately water-absorbing commercial segmented block copolymer, Hytrel(®) 8206, demonstrated selectivity toward 4VL relative to its precursor, 4HV, and increased 4VL production by approximately 30% by shifting the equilibrium toward the product. This work has shown that water absorption is an important, previously neglected criterion in evaluating polymer affinity and selectivity toward hydrophilic target molecules.