Bioconversion of hydrophobic compounds in a continuous closed-gas-loop bioreactor: Feasibility assessment and epoxide production

Microorganisms can be used as catalysts to produce organic compounds in a h ighly chemo-, regio- and enantioselective manner, and whole cells do not re quire the costly addition of cofactors for redox reactions. However, biocon versions are slow compared to alternative chemical reactions, and the bioca talyst works at its best in an aqueous medium, while the transformations of interest frequently involve compounds with a low-aqueous solubility and th at are toxic to microorganisms. This results in low-volumetric productivity in classical bioreactors. The Continuous Closed-Gas-Loop Bioreactor is des cribed here-a reactor system with high productivity, but without the proble ms associated with two-phase systems, such as an emulsified product stream and phase toxicity. Its working principle is to recirculate a gas phase thr ough a bioreaction compartment and a saturator/absorber module where the pr oduct accumulates as a clear organic solution. A wide range of bioconversio ns should be possible in this set-up, and proof of concept was established for the epoxidation of 1,7-octadiene to (R)-1,2-epoxyoct-7-ene by a native strain of Pseudomonas oleovorans. This reaction represents a group of termi nal alkene epoxidations where the bioconversion substrate does not support growth of the microorganism. Practical results at a 51-scale are presented for this bioconversion for both batch and continuous operation with respect to the aqueous phase, showing continuous stable epoxidation at productivit ies >14 mu mol min(-1) L-1 (U L-1). The results confirm that the metabolism does not allow a simple optimization strategy, because growth and biotrans formation substrates compete for the same enzyme sites, and conversely grow th on a substrate using this very enzyme system is necessary for longterm b ioconversion. Integrated removal of the CO2 formed via the liquid overflow was estimated from theory and verified in experimental work. (C) 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 70: 553-503, 2000.