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

Abstract

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