Ene‐Reductase: A Multifaceted Biocatalyst in Organic Synthesis

Abstract

Biocatalysis integrate microbiologists, enzymologists, and organic chemists to access the repertoire of pharmaceutical and agrochemicals with high chemoselectivity, regioselectivity, and enantioselectivity. The saturation of carbon-carbon double bonds by biocatalysts challenges the conventional chemical methodology as it bypasses the use of precious metals (in combination with chiral ligands and molecular hydrogen) or organocatalysts. In this line, Enereductases (ERs) from the Old Yellow Enzymes (OYEs) family are found to be a prominent asymmetric biocatalyst that is increasingly used in academia and industries towards unpar-alleled stereoselective trans-hydrogenations of activated C=C bonds. ERs gained prominence as they were used as individual catalysts, multi-enzyme cascades, and in conjugation with chemical reagents (chemoenzymatic approach). Besides, ERs' participation in the photoelectrochemical and radical-mediated process helps to unlock many scopes outside traditional biocatalysis. These up-and-coming methodologies entice the enzymologists and chemists to explore, expand and harness the chemistries displayed by ERs for industrial settings. Herein, we reviewed the last five year's exploration of organic transformations using ERs.

Biohydrogenation of 1,3-Butadiene to 1-Butene under Acetogenic Conditions by Acetobacterium wieringae

“…It has been reported that the biohydrogenation of diene compounds is catalyzed by a collection of enzyme families known as ene-reductases, such as the FMN-containing old yellow enzyme (OYE), medium-chain dehydrogenases/reductases (MDRs), and short-chain dehydrogenases/reductases (SDRs) . A variety of ene-reductases have been identified from previously untapped sources. , Such efforts have improved not only our understanding of the ecological functions and evolution of ene-reductases but also the applications of these enzymes in chemical synthesis . For instance, flavone reductase, an ene-reductase catalyzing the hydrogenation of the C2C3 bond of flavones/flavonols in the gut bacterium Flavonifractor plautii ATCC 49531, plays essential roles in gut microbial consumption and transformation of xenobiotic flavonoids .…”

“…Biocatalytic hydrogenation of BD to 1-butene by ene-reductases may be one of the promising technologies owing to the exquisite stereoselectivity, green chemistry, and sustainability . Nonetheless, applications of biocatalysis capable of hydrogenation of BD to 1-butene for industry may also be challenging (e.g., vulnerability under harsh conditions and industrial scale); thus, a mechanistic understanding of the process (e.g., cofactor dependence and enzyme structure) will be conducive to enhancing biocatalytic performance by protein engineering for future preparative and industrial applications. , …”

“…56 Nonetheless, applications of biocatalysis capable of hydrogenation of BD to 1-butene for industry may also be challenging (e.g., vulnerability under harsh conditions and industrial scale); thus, a mechanistic understanding of the process (e.g., cofactor dependence and enzyme structure) will be conducive to enhancing biocatalytic performance by protein engineering for future preparative and industrial applications. 52 The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.est.2c05683. Energetics and calculation of H 2 -consuming BD biohydrogenation and other potential H 2 -consuming processes in the BD/HCO 3 − and BD/HEPES consortia (Supplementary Method); chromatograms of the headspace samples taken from the BD-biohydrogenating sediment microcosm (Figure S1), structural confirmation of 1-butene by GC−MS with a scan range of m/z 25−60 (Figure S2), biohydrogenation of BD to 1-butene in the BD/HCO 3 − consortium without and with BES (Figure S3), microbial community profiles at the phylum level and the genus level in the BD/HCO 3 − consortium amended with acetate and H 2 (Figure S4), summary and visualization of ecosystem-relevant metabolisms across qualified MAGs assembled from the BD/HCO 3 − consortium (Figure S5), and genome-based phylogenetic tree inferred using FastME version 2.1.6.1 with GBDP (Genome Blast Distance Phylogeny) distances calculated from genome sequences (Figure S6) (PDF) Summary of the metagenome-assembled genomes from the BD/HCO 3 − consortium (Table S1) (XLSX) List of 16 putative ene-reductase genes in the draft genome of strain N (Table S2) (XLSX) ■ AUTHOR INFORMATION…”

Photosensitized Radical-Anion-Driven Metal-Free Selective Reduction of Aldehydes Using Graphene Oxide as an Electron Relay Mediator under Visible Light

“…The reduction of aromatic aldehydes is a prototypical approach to preparing aromatic alcohols. Many synthetic and catalytic practices have been probed for this fundamental transformation: − transition-metal-catalyzed hydrogenation, catalytic hydrogenation via H 2 , biocatalytic reductions, and conventional stoichiometric reagents (metal hydrides) dominate industrial- and laboratory-scale conversions. These practices suffer from poor selectivity and severe ecological concerns.…”

Chlamydomonas reinhardtii mutants deficient for Old Yellow Enzyme 3 exhibit increased photooxidative stress

“…Ene-reductases, also termed Old Yellow Enzymes (OYEs) based on their discovery as a yellow ferment in 1932 (Haas, 1938;Warburg & Christian, 1932), catalyze the NAD(P)H-dependent asymmetric reduction of activated C=C bonds (Karrer et al, 2021;Kumar Roy et al, 2022) (Figure 1a). The flavin-containing enzymes have been intensely analyzed with respect to their biochemical, biophysical, and structural properties, and their reaction mechanism is well understood (Peši c et al, 2017;Shi et al, 2020;Theorell & Åkeson, 1956;Tischler et al, 2020;Williams & Bruce, 2002).…”