An official website of the United States government
Abstract Chirality plays a significant role in the manufacture of pharmaceuticals and fine chemicals. The use of chemical catalysts to control stereoselectivity relies on the use of chiral catalysts with labor–intensive synthesis and purification. Natural enzymes offer inherent stereoselectivity, making them attractive catalysts for this purpose. We report here chiral biocatalytic oxidations in microemulsions driven by horseradish peroxidase coupled with a synthetic Cu2+‐polymer catalyst. This hybrid system features crosslinked layer–by–layer (LBL) films composed of polyions with Cu2+‐containing pyrene–labelled poly(2‐hydroxy‐3‐dipicolylamino) propyl methacrylate (Py−PGMADPA) to drive oxygen reduction to form hydrogen peroxide. Peroxide in turn activates horseradish peroxidase (HRP) crosslinked in LbL films on magnetic particle beads to biocatalytically oxidize styrene, ethylbenzene, and methyl phenylacetate to chiral products. R‐stereoisomers of these reactants were selectively formed with a high enantiomeric excess of ≥80 % at 90 °C. The enzyme films show high thermal stability at 90 °C in cetyltrimethylammonium bromide microemulsion. Reactions at 90 °C were essentially complete in 2 hr. This hybrid approach opens a door to new designs of biocatalytic syntheses using a separate electrocatalyst for enzyme activation.
more »
« less
Biocatalytic Nitration of Phenols in Microemulsions at Elevated Temperatures Using Enzymes Stabilized on Magnetic Beads
Abstract Enzymes as catalysts in organic syntheses can provide high regio‐ and stereo‐selectivity, which is often not possible with chemical catalysts. Biocatalysis with iron heme enzymes has proven efficient when the enzyme is sequestered in thin films. An added feature is improved stability. For example, peroxidases chemically crosslinked in poly‐lysine in films on silica nanoparticles were stable for 9 hrs or more at 90 °C, and were used for biocatalysis up to 90 °C. We show here for a series ofpara‐substituted phenols, single nitro‐phenol products can be selectively synthesized using biocatalytic magnetic beads coated with horseradish peroxidase (HRP) crosslinked in polylysine films. Nitrophenols moieties are important as synthetic intermediates and in drugs. For a series ofpara‐substituted phenols, biocatalytic nitration gave average turnover numbers 1.8‐fold larger at 75 °C than at 25 °C. For phenols giving <50 % conversion after 1 hr at 25 °C, twice the nitration yield was achieved in 1 hr at 75 °C. Results indicate that this approach should be valuable as a general tool for biocatalytic chemical synthesis.
more »
« less
- Award ID(s):
- 2035669
- PAR ID:
- 10422217
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- ChemCatChem
- Volume:
- 15
- Issue:
- 15
- ISSN:
- 1867-3880
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Efforts to drive catalytic reactions with light, inspired by natural processes like photosynthesis, have a long history and have seen significant recent growth. Successfully engineering systems using biomolecular and bioinspired catalysts to carry out light‐driven chemical reactions capitalizes on advantages offered from the fields of biocatalysis and photocatalysis. In particular, driving reactions under mild conditions and in water, in which enzymes are operative, using sunlight as a renewable energy source yield environmentally friendly systems. Furthermore, using enzymes and bioinspired systems can take advantage of the high efficiency and specificity of biocatalysts. There are many challenges to overcome to fully capitalize on the potential of light‐driven biocatalysis. In this mini‐review, we discuss examples of enzymes and engineered biomolecular catalysts that are activated via electron transfer from a photosensitizer in a photocatalytic system. We place an emphasis on selected forefront chemical reactions of high interest, including CH oxidation, proton reduction, water oxidation, CO2reduction, and N2reduction.more » « less
-
Cornish, Virginia; Billerbeck, Sonja (Ed.)Biocatalysis has the potential to address the need for more sustainable organic synthesis routes. Protein engineering can tune enzymes to perform in cascade reactions and for efficient synthesis of enantiomerically enriched compounds, using both natural and new-to-nature reaction pathways. This review highlights recent achievements in biocatalysis, especially the development of novel enzymatic syntheses to access versatile small molecule intermediates and complex biomolecules. Biocatalytic strategies for the degradation of persistent pollutants and approaches for biomass valorization are also discussed. The transition of chemical synthesis to a greener future will be accelerated by implementing enzymes and engineering them for high performance and new activities.more » « less
-
Abstract Billions of years of evolution have led to the selection of (hyper)thermophiles capable of flourishing at elevated temperatures. The corresponding native (hyper)thermophilic enzymes retain their tertiary and quaternary structures at near‐boiling water temperatures and naturally retain catalytically competent conformational dynamics under these conditions. And yet, while hyper/thermophilic enzymes offer special opportunities in biocatalysis and in hybrid bio/chemocatalytic approaches to modern synthesis in both academia and industry, these enzymes remain underexplored in biocatalysis. Among the strategic advantages that can be leveraged in running biocatalytic transformations at higher temperatures are included more favorable kinetics, removal of volatile byproducts to drive reactions forward, improved substrate solubility and product separation, and accelerated stereodynamics for dynamic kinetic resolutions. These topics are discussed and illustrated with contemporary examples of note, in sections organized by stratagem. Finally, the reader is alerted in particular to archaeal enzymes that have proven useful in non‐natural synthetic chemistry ventures, and at the same time is referred to a rich area of archaea whose genomes have been sequenced but whose enzymatic activities of interest have not yet been mined. Though hyperthermophilic archaea are among the most ancient of organisms, their enzymes may hold the key to many future innovations in biocatalytic chemistry–perhaps we really do need to go ‘back to the future’.more » « less
-
null (Ed.)Site-directed spin labeling (SDSL) in combination with electron paramagnetic resonance (EPR) spectroscopy probes the otherwise inaccessible structural information in complex biological systems. We recently extended SDSL-EPR to reveal the relative orientation and backbone dynamics of enzymes upon encapsulation in mesoporous nanostructures, which set the structural basis underlying the observed biocatalytic activity. Our strategy had generated interest in the biocatalysis community, and thus in this resource article, we contribute an introduction to the principles and experimental procedure that generalize SDSL-EPR to heterogeneous biocatalysis. We will focus on enzymes in mesoporous materials with examples demonstrating the methods and cautions of potential pitfalls. The ultimate goal is to provide the biocatalysis community with a powerful resource to fill in a long-standing knowledge gap in heterogeneous biocatalysis and the structure-function relationship of enzymes at the interface of enzyme-mesoporous materials and utilize the structural insights to guide the rational design of porous platforms for enzyme immobilization.more » « less
