Enantiomeric separation of pharmaceutically important drug intermediates using a Metagenomic lipase and optimization of its large scale production

In the present study, efficient enzymatic methods were developed using a recombinant metagenomic lipase (LipR1) for the synthesis of corresponding esters by the transesterification of five different pharmaceutically important secondary alcohols. The recombinant lipase (specific activity = 87m6 U/mg) showed maximum conversion in presence of ionic liquid with Naphthyl-ethanol (eeP = 99%), Indanol and Methyl-4 pyridine methanol (eeS of 98% and 99%) respectively in 1 h. Vinyl acetate was found as suitable acyl donor in transesterification reactions. It was interesting to observe that maximum eeP of 85% was observed in just 15 min with 1-indanol. As this enzyme demonstrated pharmaceutical applications, attempts were made to scale up the enzyme production on a pilot scale in a 5 litre bioreactor. Different physical parameters affecting enzyme production and biomass concentration such as agitation rate, aeration rate and inoculum concentration were evaluated. Maximum lipase activity of 8463 U/ml was obtained at 7 h of cultivation at 1 lpm, 300 rpm and 1.5% inoculum. (C) 2016 Elsevier B.V. All rights reserved.