An immersed hollow fiber membrane bioreactor for enhanced biotransformation of indene to cis-indandiol using Pseudomonas putida

• We developed an immersed membrane bioreactor for pharmaceuticals biotransformation.
• System showed enhanced cis-indandiol conversion from indene.
• Optimized operation increased product concentration by 4.5 times compared to suspension cultures.
• Membranes served to immobilize cells and sequester inhibitory indene.
• Reusability of membranes demonstrated over 5 repeated cycles.

An immersed hollow fiber membrane bioreactor (IHFMB) was fabricated for production of pharmaceutical intermediates cis-indandiol from indene by Pseudomonas putida ATCC 55687. At 2–6 g/L indene, significant increase of 160–400%, corresponding to 240–400 mg/L of cis-indandiol was achieved as compared to that obtained from suspension culture bioreactors (SCB). The IHFMB volumetric productivity of 10.1–12.9 mg/(L h) and molar yield of 0.050–0.093 mol/mol indene was also higher than the 4.3–8.3 mg/(L h) and 0.01–0.030 mol/mol indene, respectively, in the SCB. The hollow fiber membranes in the IHFMB facilitated a more effective biotransformation through reactant sequestration and cell immobilization, with equal contribution at low indene concentrations, albeit a lower contribution by the latter at 6 g/L indene. The performance of the IHFMB was further improved by process optimization and the highest product titer of 487 mg/L, overall volumetric productivity of 24.6 mg/(L h) and molar yield of 0.126 mol/mol indene were achieved with a module comprising 28 membranes (168 cm2/150 mL working volume) at a medium circulation rate of 5 mL/min and aeration rate of 0.5 vvm. Reusability of the membranes has also been successfully demonstrated through 5 successive operations of batch biotransformation.