Manipulating enzymes using molecular scaffolding

ChemSci Pick of the Week

Our ChemSci Pick of the Week describes a new way to use “molecular scaffolding” to manipulate enzymatic reactions, which could be used for efficient industrial processes.

Enzymes are natural catalysts which can be used on an industrial scale to replace traditional chemical synthesis. Using these natural systems has sustainable benefits including reduced emissions of greenhouse gases, while lowering energy input, water consumption and waste production.

Enzymatic reactions often occur at room temperature and pressure in water; therefore being able to make tailored enzymes could have wide-ranging benefits for the food, cosmetic and pharmaceutical industries.

Corresponding author Sophie Beeren, from Technical University of Denmark, described the work as "a conceptually new way of exploiting enzymes".

Using the analogy of building a Roman archway using a scaffold, where the shape of the wooden scaffold would determine the shape of the stone structure, Beeren explained how their method of template synthesis works on a molecular scale.

"Our building blocks are sugar monomers. The scaffolding is a molecular guest, or template. We glue the building blocks together using enzyme-catalysed reactions. The shape of the template determines how the building blocks end up glued together and thus 'selects' permutation and combinations of building blocks.

"We use different small synthetic molecules to control an enzyme-catalysed reaction and obtain selectively different products, including different ones to those obtained in nature."

Specifically, the authors made various types of sugar called cyclodextrins which are used extensively in foods, cosmetics, food production and drug delivery. They bind small hydrophobic molecules, making them soluble and stable in water.

"There are three that are produced industrially, CD6, CD7, CD8," Beeren said. "Using templates we can access CD9 and CD10 and potentially in the future even larger cyclodextrins. These could potentially be used as molecular hosts for similar applications in the future, but also for larger molecules that don’t fit inside the existing CD hosts.

"More broadly speaking, we propose that enzymes can be exploited to catalyse reactions reversibly, generate mixtures of interconverting oligomers from which different products can be selected by adding different templates. This could lead to novel uses of enzymes for the production of fine chemicals and biopolymers."

This article is free to read in our open access, flagship journal Chemical Science: Dennis Larsen and Sophie R Beeren, Chem. Sci., 2019, Advance Article. DOI: 10.1039/C9SC03983J. You can access our 2019 ChemSci Picks in this article collection.