Molecular Basis of Aqueous-like Activity of Lipase Treated with Glucose-Headed Surfactant in Organic Solvent

Abstract

Lipases are useful as catalysts, particularly for the kinetic resolution of racemic alcohols and esters. However, their industrial applications are limited by their poor activities in organic media. We recently found that a lipoprotein lipase from Burkholderia species displays dramatically enhanced activity in organic solvent if the protein is coated with glucose-headed surfactant (GHS). Here we investigate the molecular basis of this enhanced enzymatic activity in organic solvent by performing molecular dynamics simulations on Burkholderia cepacia lipase as a model enzyme. Our simulation results indicate that the enhanced activity of lipase stems from a dual function of GHSs different in water and organic solvent. GHS molecules maintain the open conformation of lipase by providing lipid-like microenvironment surrounding the active site in water and stabilize its native active conformation by providing water-like microenvironment around the surface of the lipase in the organic solvent. Our data also suggest the role of organic cosolvent that can facilitate closed-to-open conformational changes during the freeze-drying process. The computational approach in this study lays its potential for guiding the design of more effective surfactant molecules to improve the activity of lipases in organic solvent.