Hydrolases: catalytically promiscuous enzymes for non-conventional reactions in organic synthesis

Abstract

During the last three decades the use of hydrolases for the catalysis of environmentally friendly organic processes under mild reaction conditions has been well documented. Hydrolases have shown themselves to be ideal tools for the acceleration of synthetic transformations because of their high stability, catalytic efficiency, commercial availability and broad substrate specificity in a wide spectrum of biocatalyzed processes. In recent years, novel examples have appeared related to non-conventional reactions catalyzed by hydrolytic enzymes. Amongst these, lipases and acylases have gained much attention as promiscuous biocatalysts showing good levels of reactivity in C-C bond formation, C-heteroatom bond formation, oxidative processes, and novel hydrolytic reactions. This critical review covers recent investigation in the field of catalytic promiscuity, and highlights the most surprising and uncommon activities that this class of enzymes shows in organic synthetic transformations (111 references).

Lipase-Catalyzed Kinetic Resolution of 1-(2-Hydroxycyclohexyl)Indoles in Batch and Continuous-Flow Systems

“…[29][30][31][32][33][34][35][36][37][38] The production of chiral alcohols brought in 2002 more than 7 billion dollars in revenues worldwide and this was forecasted to be 14.9 billion dollars by the year 2009. 39 Although a tremendous number of biocatalytic reactions have been studied, [16][17][18][20][21][22][23][24][25][26] the operational parameters reported for most of them seem to be rather suboptimal. Therefore, there is still much room for optimization promoting thereby faster transfer to an industrial scale.…”

“…Hydrolases, especially lipases are among the most often used enzymes for synthetic purposes. 20 Lipases have been used for numerous stereoselective biotransformations [21][22][23][24][25][26] such as kinetic resolution (KR) 20,27 , deracemisation and dynamic kinetic resolution (DKR) 30 due to their high regio-, chemo-and enantioselectivity, high stability, compatibility of organic solvents, wide substrate range, and because they do not need co-factors. Lipases -either in their native form or tailored by genetic engineering -are ideally suited for industrial applications, 17,28 preferably in their immobilised forms to enable recycling.…”

Use of high activity enzyme preparations in neat organic solvents for organic synthesis

“…Hydrolases, especially lipases, have been the focus of attention in many studies which report catalysis of C-C bond or C-heteroatom bond. Larger percentage of these studies has involved aqueous-organic co-solvent mixtures as reaction medium rather than nearly anhydrous organic solvents [70]. However, some interesting results in low water containing organic solvents as reaction medium have also been reported.…”

“…While doi: 10.7243/2053-7670-1-1 considerable amount of work has been already reported on "induced catalytic promiscuity" which involves enzymes engineered by protein engineering and directed evolution methods [69,70] we will again restrict ourselves to "accidental catalytic promiscuity" shown by wild enzymes in low water containing organic solvents. As Busto et al, (2010) [70] have recently reviewed this as well extensively, only brief treatment will be provided here with a focus on the current status of catalytic efficiency in such cases. Hydrolases, especially lipases, have been the focus of attention in many studies which report catalysis of C-C bond or C-heteroatom bond.…”

Catalytic Promiscuity of Transaminases: Preparation of Enantioenriched β‐Fluoroamines by Formal Tandem Hydrodefluorination/Deamination

“…This catalytic promiscuity [1] can be useful for synthetic purposes, broadening the applicability of biocatalysts. While many examples have recently been described for hydrolases, [2] the application of these unconventional processes for other enzyme classes has not been fully developed. [3] Among biocatalysts that have demonstrated broad applicability, transaminases (TAs) can be highlighted, as they perform the amination of an amine acceptor (ketone or aldehyde) using an amine donor (e.g., alanine or isopropylamine, Scheme 1a), mediated by the cofactor pyridoxal 5'-phosphate (PLP).…”