The coupling of an enzyme with a light-activated catalyst offers great potential for organic synthesis. Catalysts working in pairs can promote more-effective reactions than can the same catalysts used sequentially. The study was published in the journal Nature.

The development of catalytic reactions is a dominant theme in chemistry, especially in industry, where major efforts are underway to develop large-scale chemical processes that are sustainable and avoid producing unnecessary waste. Chemical reactions can be accelerated using many types of catalyst, including metals (or their salts or complexes), small organic molecules, enzymes and light-activated catalysts.

Catalysts of all types have advanced to the extent that two or more catalysts can be combined to promote cascade reactions interconnected transformations, carried out in a single operation, to yield products with selectivities that would be difficult to achieve using the catalysts independently in sequential steps.

They report that the combination of an enzyme with a light-activated catalyst starts a cascade reaction that produces compounds that are versatile intermediates for organic synthesis. The use of combinations of catalysts could potentially lead to step changes in the efficiency of chemical processes.

Enzymes Combination

Certain combinations of enzymes with small-molecule organic catalysts or transition-metal catalysts have been of particular interest in part because the chemistry mediated by these different catalyst types is highly complementary, and also because water is used as the main solvent, thus avoiding environmentally harmful organic alternatives. 

Although methods exist that allow just one isomer of an alkene to be produced during synthesis, it is often cheaper and easier to prepare alkenes as mixtures of (E)- and (Z)-isomers. But using such mixtures can be problematic. Alkenes are often chemically reduced during organic syntheses that are, the carbon-carbon double bonds are converted into single bonds. 

Reductase Enzymes

In the current study, they combined analogs of those iridium photocatalysts with one reductase enzymes, which reduce alkenes and are generally (E)-selective, although the authors also tested a (Z)-selective one reductase in their system.

Enzyme's Cofactor

The researchers optimized various parameters of their reactions, including the concentrations of the iridium catalyst, the enzyme, and the enzyme’s cofactor. They developed a system that reduces mixtures of (E)- and (Z)-isomers of alkenes to form a single stereoisomer, in multi-milligram quantities.

The authors went on to convert the stereoisomer into a variety of biologically active molecules and key intermediates that have been used to prepare such molecules, thereby highlighting the potential application of their chemistry for preparative organic synthesis.

Photocatalysts also often work through mechanisms that generate intermediates that are stable in the presence of water and tolerant of the chemical groups found in enzymes. Therefore, photocatalysts, in general, might be particularly suitable for being combined with enzymes for synthetic reactions.

Even if the enzyme does not work under conditions demanded by industry, or for a broad range of substrates, all is not lost. Techniques such as protein engineering and directed evolution are increasingly being used to rapidly optimize the characteristics of enzymes to make them compatible with industrial processes.

Chemical Catalysts

Indeed, enzymes are the ultimate tunable catalysts, and will therefore surely be combined with many other chemical catalysts in the future.