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This breakthrough could lead to cleaner, more efficient ways of making medicines and other important chemicals, all while reducing the need for harsh chemicals and harmful ultraviolet (UV) light. The discovery, which represents a major step forward in the field of photocatalysis - using light to drive chemical reactions - shows how biology and chemistry can work hand-in-hand to unlock new possibilities for safer, greener manufacturing.

Swapping harmful UV for everyday visible light

Many light-driven chemical processes rely on UV light and chemical helpers called Çà¹ÏÊÓƵ˜sensitisersÇà¹ÏÊÓƵ™, which absorb the light and transfer the energy to the other molecules to drive the reaction. Previous research from the MIB had selectively introduced UV sensitisers into proteins that resulted in photoenzymes that were more efficient, selective and versatile than traditional small molecule sensitisers. However, these UV-driven photoenzymes have downsides: they suffer from low photochemical efficiencies, can damage delicate molecules, and often produce unwanted by-products, therefore limiting the scope of possible reactions.

To address these issues, Dr Rebecca Crawshaw and Dr Ross Smithson, part of the Green Group, led by , engineered enzymes that contain a different type of light-absorbing molecule called thioxanthone. Unlike older sensitisers, thioxanthone works with visible light, making the system not only more efficient but also more environmentally friendly and compatible with industrial lighting conditions.

Improved efficiency from a nature-inspired design

By embedding these thioxanthone sensitisers directly into enzymes, the scientists have created new Çà¹ÏÊÓƵ˜photoenzymesÇà¹ÏÊÓƵ™ that can perform light-powered reactions with remarkable speed and accuracy.

One of these enzymes, named VEnT1.3, was able to produce its target chemical with significantly improved efficiencyÇà¹ÏÊÓƵ”completing over 1,300 reaction cycles and doing so with precise control over the arrangement of atoms. This level of control is especially important when making pharmaceuticals, where the 3D shape of a molecule can mean the difference between a life-saving drug and an ineffective or harmful substance.

The new photoenzymes also open new pathways for manufacturing as they can achieve chemical reactions that would be difficult, or even impossible, to do using traditional chemical methods. For example, the team developed a second enzyme, called SpEnT1.3, which can build complex ring-shaped molecules known as spirocyclic β-lactams. These are important building blocks for medicines and other high-value chemicals.

Additionally, the photoenzymes can also suppress undesired decomposition pathways that commonly plague small-molecule photocatalysis. These findings highlight the unique capability of engineered enzymes to govern the fate of reactive intermediates with a level of control that remains out of reach for conventional catalysts.

A greener future for chemical manufacturing

The success of this genetic encoding approach underscores the broader potential of using engineered enzymes as a flexible platform for visible-light photocatalysis. By expanding the genetic code to incorporate novel sensitisers like thioxanthone, researchers can fine-tune photoenzyme scaffolds for a wide array of reactionsÇà¹ÏÊÓƵ”alleviating many of the limitations imposed by more traditional photocatalysts.

The research also highlights the power of combining cutting-edge science from different fieldsÇà¹ÏÊÓƵ”genetic engineering, chemistry, and biologyÇà¹ÏÊÓƵ”to solve practical problems. By expanding the genetic Çà¹ÏÊÓƵ˜toolkitÇà¹ÏÊÓƵ™ that scientists use to build enzymes, the team can design these biological catalysts to do exactly whatÇà¹ÏÊÓƵ™s needed, in the right place, at the right time.

Such advances could ultimately facilitate the design of enzyme systems capable of performing complex photochemical transformations with unmatched precision and efficiencyÇà¹ÏÊÓƵ”benefiting sectors ranging from pharmaceuticals and agrochemicals to materials science and beyond.