Designing Enzymes from Scratch: A Breakthrough in Chemistry

Researchers at UC Santa Barbara, UCSF, and the University of Pittsburgh have made a groundbreaking discovery in chemistry, enabling the design of enzymes from scratch. This breakthrough has far-reaching implications for various fields, including drug development, materials science, and biotechnology.

According to Professor Yang Yang, a senior author on the paper, “If people could design very efficient enzymes from scratch, you could solve many important problems.” De novo enzyme design can overcome limitations in function and stability found in natural catalysts without losing their inherent selectivity and efficiency.

Catalysts, both biological and synthetic, are the backbone of chemistry. They accelerate reactions that change the structures of target molecules. Enzymes, in particular, are “nature’s privileged catalysts” due to their high level of selectivity and efficiency. However, natural enzymes tend to function under narrow conditions, favoring specific molecules and environments.

To address this limitation, scientists have turned to de novo protein design – a bottom-up approach that uses amino acid building blocks to create proteins with specific structures and functions. De novo proteins are relatively small, which provides favorable efficiency relative to most enzymes. They also exhibit excellent thermal and organic solvent stability, allowing for wider temperature ranges and up to 60% of organic solvents.

The researchers demonstrated their proof-of-concept by using de novo protein design to create enzymes that can form carbon-carbon or carbon-silicon bonds – a challenging transformation that requires efficient natural enzymes. They used a helical bundle protein as a framework, which they then modified using state-of-the-art artificial intelligence methods to design sequences of amino acids with the desired functionalities and properties.

The initial results showed reasonable catalysts but not the best due to modest efficiency and selectivity. However, after a second round of design using a loop searching algorithm, four out of 10 designs exhibited high activity and excellent stereoselectivity.

This breakthrough demonstrates that de novo protein design can be a powerful tool in catalysis, offering chemists more efficient and selective reactions as well as products that aren’t easily reached with natural enzymes or small-molecule synthetic catalysts. Further work will involve exploring ways to mimic natural enzyme function with simpler, smaller but equally active de novo enzymes and generating de novo enzymes that operate via mechanisms not previously known in nature.

Research in this paper was conducted by Kaipeng Hou, Wei Huang, Miao Qui, Thomas H. Tugwell, Turki Alturaifi, Yuda Chen, Xingjie Zhang, Lei Lu, and Samuel I. Mann.

The University of Wisconsin-Madison engineers have successfully created a cutting-edge, high-performing heat exchanger by combining topology optimization and additive manufacturing techniques. This innovative approach has led to a heat exchanger with an intertwining design that significantly outperforms its traditional counterpart in terms of heat transfer and power density.

Traditionally, heat exchangers have been designed with straight channels due to ease of manufacture. However, this new design breaks away from convention by incorporating complex geometries that guide fluid flow in a twisting path, resulting in enhanced heat transfer capabilities.

The optimized design, led by Professor Xiaoping Qian, has achieved a 27% higher power density compared to the traditional heat exchanger. This increase in power density enables the heat exchanger to be lighter and more compact, making it ideal for applications in aerospace, power generation, and industrial processes.

The team’s research was published in the International Journal of Heat and Mass Transfer and has been patented through the Wisconsin Alumni Research Foundation. The work was supported by grants from ARPA-E and the National Science Foundation.

This breakthrough is a testament to the innovative potential of combining topology optimization and additive manufacturing techniques. It demonstrates that, with careful design and consideration for manufacturability constraints, it’s possible to create high-performance heat exchangers that can significantly improve efficiency in various industries.

The pursuit of efficient energy storage has led scientists to explore novel materials for solid-state batteries. Researchers at TUM and TUMint.Energy Research have taken a groundbreaking step forward by developing a new material that conducts lithium ions more than 30% faster than any previously known substance. This breakthrough, achieved through the creation of a lithium-antimonide compound with scandium, has far-reaching implications for the future of energy storage.

The team, led by Prof. Thomas F. Fässler from the Chair of Inorganic Chemistry with a Focus on Novel Materials, discovered that by partially replacing lithium in a lithium antimonide compound with the metal scandium, they could create specific gaps or vacancies in the crystal lattice of the conductor material. These gaps allowed the lithium ions to move more easily and faster, resulting in an unprecedented level of ion conductivity.

To validate this result, the team collaborated with the Chair of Technical Electrochemistry under Prof. Hubert Gasteiger at TUM. Co-author Tobias Kutsch, who conducted the validation tests, noted that the material also conducts electricity, presenting a special challenge for measurement methods.

Prof. Fässler sees great potential in the new material: “Our result currently represents a significant advance in basic research. By incorporating small amounts of scandium, we have uncovered a new principle that could prove to be a blueprint for other elemental combinations.” The team is optimistic about the practical applications of this discovery, particularly as additives in electrodes.

In addition to its faster conductivity, the material also offers thermal stability and can be produced using well-established chemical methods. The researchers believe that their combination of lithium-antimony could have broader implications for enhancing conductivity in a wide range of other materials.

The team has even discovered an entirely new class of substances through their work, as first author Jingwen Jiang emphasizes: “Our combination consists of lithium-antimony, but the same concept can easily be applied to lithium-phosphorus systems. While the previous record holder relied on lithium-sulphur and required five additional elements for optimization, we only need Scandium as an additional component.”

This breakthrough has the potential to revolutionize energy storage, making it more efficient and sustainable for a wide range of applications. The researchers’ enthusiasm is evident in their pursuit of further testing and validation, with the goal of integrating this new material into practical battery cells.