Biocatalytic Friedel–Crafts Alkylation Using a Promiscuous Biosynthetic Enzyme

Abstract

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BrtB is an O-alkylating enzyme that generates fatty acid-bartoloside esters

“…We set out to investigate whether BrtB, the only enzyme in the brt gene cluster with no ascribed function, could be responsible for ester formation. Following the protocol reported by Schultz et al 15 , we expressed and purified a Strep-Tag©-recombinant version of BrtB (NStrep-BrtB) in Escherichia coli BL21 DE3 Rosetta cells and tested its ability to convert 1 and 2 into 3 in vitro. We found that adding NStrep-BrtB to a reaction mixture composed of 1, 2 and Ca 2+ and Mg 2+ -containing buffer 12,15 was necessary and sufficient to generate diester 3 as well as monoester(s) 6a and/or 6b (Fig.…”

“…However, the role played by the brt-encoded CylK homolog (BrtB) has remained unclear. The reasons for this are twofold: first, the action of a CylK homolog is not necessary to explain the biosynthesis of currently known bartolosides 13,14 ; second, CylK requires a free C-2 resorcinol as a nucleophile 12,15 , a position that is unavailable (it is alkylated) in the bartolosides. Here, we show that BrtB is an O-alkylating enzyme that catalyzes the esterification of free (non-activated) fatty acids with the chlorinated positions found in the bartolosides, generating a diversity of fatty acid-bartoloside esters (Fig.…”

Thermal and Mechanical Stability of Immobilized Candida antarctica Lipase B: an Approximation to Mechanochemical Energetics in Enzyme Catalysis.

“…Enzymes are potent biocatalysts that are able to carry out numerous chemical transformations with remarkable chemo‐, regio‐ and stereo‐selectivity . The intrinsic sustainability of enzymatic processes along with the use of green reaction conditions such as absence of potentially toxic solvents, and activation with non‐conventional sources of energy has expanded the use of biocatalysis in both chemical industries and in academic institutions, focusing in drug discovery and in the synthesis of molecules with relevant biological activity .…”

“…Enzymes are potent biocatalysts that are able to carry out numerous chemical transformations with remarkable chemo-, regio-and stereo-selectivity. [1][2][3][4][5] The intrinsic sustainability of enzymatic processes along with the use of green reaction conditions such as absence of potentially toxic solvents, and activation with non-conventional sources of energy has expanded the use of biocatalysis in both chemical industries and in academic institutions, focusing in drug discovery and in the synthesis of molecules with relevant biological activity. [6][7][8] Recent developments in protein engineering and enzyme directed evolution, [9,10] together with the availability of efficient methods for the production of recombinant molecules, have led to rapidly expanding new fields in biocatalysis.…”

The Steric Effect in Green Benzylation of Arenes with Benzyl Alcohol Catalyzed by Hierarchical H-beta Zeolite

“…Friedel-Crafts alkylation has been an important method for preparing substituted aromatics from the past to the present days [1][2][3]. Among these classical, but practical alkylation reactions, the homogeneous benzylation of aromatic hydrocarbons by benzyl alcohol (BzOH) or benzyl chloride (BzCl) is one of the significant reaction processes for the preparation of diphenylmethane (DPM) and its substituted derivatives (Scheme 1).…”