Abstract
Lipases, a versatile class of biocatalysts, have been shown to function in non-aqueous media/organic solvents and to possess “promiscuous” catalytic activity for a wide range of organic transformations. In this study, we explored the biocatalytic properties of a library of commercially available lipases by screening them for catalysis of a one-pot synthesis of Wieland–Miescher ketone, an important intermediate in the synthesis of biologically active compounds such as steroids and terpenoids, from methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. As a direct outgrowth of this screen, we created an optimized procedure for Wieland–Miescher ketone (WMK) synthesis using crude lipase preparations, characterizing both reaction yield and enantiomeric excess. We also identified principal components of the crude lipase mixture through proteomics and present evidence for a non-lipolytic origin of the observed catalysis. Finally, using the optimized conditions developed in this study, we propose a general absorbance-based screening methodology for assessing biocatalytic potential of crude enzyme preparations for synthesis of WMK.
Highlights
Metal-based catalysts have revolutionized synthetic chemistry, enabling challenging chemical reactions with exquisite stereochemical control [1,2]
Biocatalytic potential the lipase library was theninassessed for synthesis of the Wieland–Miescher ketone from methyl of vinyl lipase was assessed for synthesis ofusing the Wieland–Miescher from conditions methyl vinyl[12]
In addition to select lipases from our initial we discovered that absorbance, in addition to mass spec, could be an effective means of screening for screen, we included commercially available proteins that were identified by proteomics as biocatalytic potential towards the Wieland–Miescher ketone (WMK) synthesis
Summary
Metal-based catalysts have revolutionized synthetic chemistry, enabling challenging chemical reactions with exquisite stereochemical control [1,2] Disadvantages of their frequent use, include high cost and potentially adverse environmental effects. A versatile class of biocatalysts, have undergone extensive study over the past two decades [5] They have been reported to function in non-aqueous media/organic solvents, possess catalytic activity towards a wide range of organic reactions, and provide recyclability via immobilization [1,5,6,7]. In their native (biological) setting, lipases catalyze the hydrolysis of esters from triacylglycerides. Some studies have identified crude lipase preparations with biocatalytic properties presuming, but not demonstrating, that lipase, in particular the lipase active site responsible for the in vivo hydrolysis of fatty acids (Figure 1A,B), is responsible for promiscuous biocatalytic behavior observed in organic or aqueous/organic solvent2020, mixtures
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