Bioproduction of cis‐(1S,2R)‐indandiol, a chiral pharmaceutical intermediate, using a solid–liquid two‐phase partitioning bioreactor for enhanced removal of inhibitors

The use of high pressure CO2‐facilitated pH swings to enhance in situ product recovery of butyric acid in a two‐phase partitioning bioreactor

“…To be competitive with petrochemically derived organic acids, cost reduction is a critical consideration (Kurzrock and Weuster‐Botz, ), and both increased biological performance and improved acid recovery would generate significant benefits, whether through increased productivity, or reduced separation costs. Solid–liquid two‐phase partitioning bioreactors (TPPBs) (Daugulis et al, ) can be used to achieve both these goals simultaneously, by absorbing an end‐product into an inexpensive, easy‐to‐handle absorptive polymer phase, which is typically added directly to the bioreactor, achieving in situ product recovery (ISPR) (Craig and Daugulis, ; Dafoe and Daugulis, ; Daugulis, ; Khan and Daugulis, ; Morrish and Daugulis, ; Peterson and Daugulis, ; Prpich and Daugulis, ). Aside from the ease of recovery afforded by physical separation of solid polymers from fermentation broth, the reduction of end‐product concentrations reduces end‐product inhibition (EPI) during a fermentation, which in turn can improve productivities, yields and titers.…”

Demonstration of in situ product recovery of butyric acid via CO2‐facilitated pH swings and medium development in two‐phase partitioning bioreactors

“…In terms of solute affinity, previous work has highlighted good partitioning of hydrophilic target molecules into polyether copolymers such as Pebax® (Arkema) and Hytrel® (DuPont), both polyether block copolymers with polyamides and polybutylene terephthalate (PBT) as respective hard segments (Dafoe and Daugulis, ; Gao and Daugulis, ; Hepburn and Daugulis, ; Prpich and Daugulis, ). In this study, three grades of Pebax® (Grades 2533, 1074, and 1657) were tested based on differences in their hard and soft segments, as well Hytrel 3078.…”

“…Partitioning coefficients (P) for butyric acid were determined using methods outlined elsewhere (Dafoe and Daugulis, ), with the additional step of weighing polymers after partitioning tests to determine water absorption to allow for correction of aqueous volume at equilibrium. Hildebrand solubility parameters of the soft segments of all polymers (Brandrup et al, ) were used as a measure to compare predicted polymer affinity for butyric acid to observed partitioning.…”