R.B. Leveson-Gower

Nature Chemistry, Published online: 10 August 2023; doi:10.1038/s41557-023-01287-x

The design and improvement of enzymes based on physical principles remain challenging. Now, the vibrational Stark effect has been used to demonstrate how an electrostatic model can unify the catalytic effects of distinct chemical forces in a quantitative manner and guide the design of enzyme variants that outperform their natural counterpart.

Nature, Published online: 08 August 2023; doi:10.1038/s41586-023-06507-5

Bonding wood with uncondensed lignins as adhesives

Nature, Published online: 02 August 2023; doi:10.1038/d41586-023-02457-0

Massive vertebrae and other fossilized remains found in Peru point to an Eocene-epoch beast of colossal proportions.

Proceedings of the National Academy of Sciences, Volume 120, Issue 31, August 2023.

Nature Reviews Chemistry, Published online: 31 July 2023; doi:10.1038/s41570-023-00523-9

To combat worsening environmental crises, chemistry needs a redesign. We see the need for a triple focus on efficiency, safety and circularity as a prerequisite for chemistry to serve sustainability and ensure that essential chemical products and processes are waste-free, functional and safe for both humans and the environment.

Nature Catalysis, Published online: 31 July 2023; doi:10.1038/s41929-023-00994-5

The generation of nitrogen-centred radicals and their subsequent reaction with control of stereoselectivity is a difficult task in synthetic chemistry. Now, the photoenzymatic production of nitrogen-centred radicals and their use in challenging enantioselective intermolecular radical hydroaminations is reported.

Isonitrileproline (Inp) is introduced as the first isonitrile-containing amino acid for solid-phase peptide synthesis. The conformation directing properties of the isonitrile group and its effect on the collagen triple helix were elucidated. The value of Inp for peptide derivatization was showcased by a chemoselective ligation with a functional chlorooxime.

Abstract

Functional groups that allow for chemoselective and bioorthogonal derivatization are valuable tools for the labelling of peptides and proteins. The isonitrile is such a group but synthetic methods for its incorporation into peptides by solid-phase peptide synthesis are not known. Here, we introduce (4S)- and (4R)-isonitrileproline (Inp) as building blocks for solid-phase peptide synthesis. Conformational studies of (4S)- and (4R)-Inp and thermal stability analysis of Inp-containing collagen triple helices revealed that the isonitrile group exerts a stereoelectronic gauche effect. We showcase the value of Inp for bioorthogonal labelling by derivatization of Inp-containing collagen model peptides (CMPs). Dual labelling with a pair of bioorthogonal reactions of a CMP containing Inp and azidoproline residues further highlights the versatility of the new isonitrile-containing amino acids.

Science, Volume 381, Issue 6656, Page 444-451, July 2023.

Bioelectrocatalytic synthesis represents an exciting merger of selective biocatalysis and green electrochemical methods for the synthesis of value-added chemicals. In this review we introduce the key concepts and vital applications of both enzymatic and microbial electrosynthetic systems.

Abstract

Bioelectrocatalytic synthesis is the conversion of electrical energy into value-added products using biocatalysts. These methods merge the specificity and selectivity of biocatalysis and energy-related electrocatalysis to address challenges in the sustainable synthesis of pharmaceuticals, commodity chemicals, fuels, feedstocks and fertilizers. However, the specialized experimental setups and domain knowledge for bioelectrocatalysis pose a significant barrier to adoption. This review introduces key concepts of bioelectrosynthetic systems. We provide a tutorial on the methods of biocatalyst utilization, the setup of bioelectrosynthetic cells, and the analytical methods for assessing bioelectrocatalysts. Key applications of bioelectrosynthesis in ammonia production and small-molecule synthesis are outlined for both enzymatic and microbial systems. This review serves as a necessary introduction and resource for the non-specialist interested in bioelectrosynthetic research.

Introducing new abiotic chemistry into living cells is a grand challenge in the field of chemical biotechnology. Here, we show that phosphate and/or biogenic amines mediate the non-enzymatic α-methylenation of butyraldehyde under biocompatible reaction conditions and can be interfaced with butyraldehyde biosynthesis from D-glucose in the bacterium Escherichia coli.

Abstract

Small molecule organocatalysts are abundant in all living organisms. However, their use as organocatalysts in cells has been underexplored. Herein, we report that organocatalytic aldol chemistry can be interfaced with living Escherichia coli to enable the α-methylenation of cellular aldehydes using biogenic amines such as L-Pro or phosphate. The biocompatible reaction is mild and can be interfaced with butyraldehyde generated from D-glucose via engineered metabolism to enable the production of 2-methylenebutanal (2-MB) and 2-methylbutanal (2-MBA) by anaerobic fermentation, and 2-methylbutanol (2-MBO) by whole-cell catalysis. Overall, this study demonstrates the combination of non-enzymatic organocatalytic and metabolic reactions in vivo for the sustainable synthesis of valuable non-natural chemicals that cannot be accessed using enzymatic chemistry alone.

Nature Catalysis, Published online: 20 July 2023; doi:10.1038/s41929-023-00986-5

Controlling the stereoselectivity in free-radical-mediated reactions is challenging. Now, a metalloredox biocatalysis strategy is reported that uses engineered cytochrome P450 enzymes for the unnatural asymmetric radical cyclization of α-haloesters to arenes.

Proceedings of the National Academy of Sciences, Volume 120, Issue 29, July 2023.

Nature, Published online: 11 July 2023; doi:10.1038/s41586-023-06415-8

De novo design of protein structure and function with RFdiffusion

Nature Catalysis, Published online: 13 July 2023; doi:10.1038/s41929-023-00979-4

The direct regioselective oxidation of internal alkenes to ketones poses an important synthetic challenge. Now, directed evolution of a cytochrome P450 enzyme affords a ketone synthase that can efficiently oxidize internal arylalkenes directly to ketones with high chemo- and regioselectivity.