The paper in Nature is here: go.nature.com/2wexBfY

Chemoenzymatic processes comprise multiple chemical reactions catalyzed by a combination of chemical catalysts and enzymes. Such processes are difficult to create because of the difference in temperature and solvents of most reactions catalyzed by chemical catalysts and by enzymes. This work describes a new strategy for the development of chemoenzymatic processes, particularly cooperative chemoenzymatic processes. Instead of driving the chemical process thermally, the chemical process – in this case an equilibration between geometric isomers of an alkene – is driven by light. By doing so, the chemical reaction occurs at temperatures and in a medium – room temperature and aqueous buffer – required for stereoselective enzymatic reactions of the product of the chemical process. This strategy could be envisioned to enable a wide range of chemoenzymatic processes for various multistep processes.

Living organisms generate complex natural products from simple chemical precursors through simultaneous reactions that are catalyzed by mutually compatible enzymes. Many of these enzymes have been refined by evolution to be both highly active and highly selective. In contrast, artificial organic total syntheses of natural products consist of sequential reactions with intermediate purification steps that cause these syntheses to be labor intensive, to generate large quantities of waste, and to generate products in low overall yields. 

To increase the efficiency of organic synthesis, chemists have developed “chemoenzymatic processes” and “(chemo)enzymatic cascades” to emulate and improve upon segments of biosynthetic pathways. Chemoenzymatic processes employ at least one enzyme and one chemical catalyst to enable an overall synthetic transformation. Ideally, these reactions combine the reactivity of chemical catalysts with the selectivity of enzymes to generate valuable products. Cooperative chemoenzymatic processes generate products in yield or selectivities or both that cannot be obtained from the sequential reactions of the individual catalytic reactions. This unique feature of cooperative processes makes them the most valuable type of chemoenzymatic process.  However, cooperative chemoenzymatic processes are difficult to develop because chemical and enzymatic catalysts generally operate in different media at different temperatures and can deactivate each other. As a result, the scope of cooperative chemoenzymatic processes that has been reported over the last 30 years has been narrow. 

In this work, we report a new class of cooperative chemoenzymatic reactions that combine photocatalyzed alkene isomerization with ene-reductases that selectively reduce carbon-carbon double bonds. This method enables the stereoconvergent reduction of E/Zmixtures of alkenes or reduction of the unreactive stereoisomer of an alkene in yields and enantiomeric excesses that match those obtained from the reduction of the pure, more reactive isomer. To corroborate our claims, a series of extensive control experiments were conducted and documented in the supporting information of our manuscript. 

This new cooperative system overcomes the limitations of both individual catalysts and affords a range of synthetically valuable and biologically active enantioenriched compounds. As noted above, these results most generally show that the compatibility between photocatalysts and enzymes broadens the scope of chemoenzymatic processes and, in the current work, provides a general strategy for converting stereoselective enzymatic reactions into stereoconvergent ones. We hope that this system will inspire the development of future cooperative processes and be incorporated into novel chemoenzymatic cascades.

The link to the article in Nature is here: https://rdcu.be/4z1K

Written by Zachary C. Litman, Yajie Wang, Huimin Zhao, and John F. Hartwig