Microbial transformations 59: first kilogram scale asymmetric microbial Baeyer-Villiger oxidation with optimized productivity using a resin-based in situ SFPR strategy.
This study is demonstrating the scale up of asymmetric microbial Baeyer-Villiger oxidation of racemic bicyclo[3.2.0]hept-2-en-6-one (1) to the kilogram scale using a 50 L bioreactor. The process has been optimized with respect to bottlenecks identified in downscaled experiments. A high productivity was obtained combining a resin-based in situ substrate feeding and product removal methodology (in situ SFPR), a glycerol feed control, and an improved oxygenation device (using a sintered-metal sparger). As expected both regioisomeric lactones [(-)-(1S,5R)-2 and (-)-(1R,5S)-3] were obtained in nearly enantiopure form (ee > 98%) and good yield. This represents the first example of such an asymmetric Baeyer-Villiger biooxidation reaction ever operated at that scale. This novel resin-based in situ SFPR technology therefore clearly opens the way to further (industrial) upscaling of this highly valuable (asymmetric) reaction.
Hilker
Iris
I
Groupe Biocatalyse et Chimie Fine, FRE CNRS 2712, Université de la Méditerranée, Faculté des Sciences de Luminy, Case 901, 163 avenue de Luminy, 13288 Marseille Cedex 9, France.
Wohlgemuth
Roland
R
Alphand
Véronique
V
Furstoss
Roland
R
D001698:Biomedical Engineering / Q000295:instrumentation / Q000379:methods; D019149:Bioreactors; D001711:Biotransformation; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism*; D002384:Catalysis; D002849:Chromatography, Gas; D005285:Fermentation; D005990:Glycerol / Q000378:metabolism; D007218:Industrial Microbiology; D010084:Oxidation-Reduction; D012117:Resins, Synthetic; D013237:Stereoisomerism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D012117:Resins, Synthetic; C419322:bicyclo(3,2,o)hept-3-en-6-one; D005990:Glycerol