Biocatalytic Oxidation Processes in Organic Synthesis

Biocatalytic oxidation harnesses specialised enzymes to introduce oxygen into organic substrates with high precision under mild conditions. Central to this field are flavin-dependent monooxygenases (FDMOs) and Baeyer–Villiger monooxygenases (BVMOs), which catalyse transformations ranging from ketone oxygenation to sulfoxide formation. These catalysts employ molecular oxygen and nicotinamide cofactors to achieve regio-, chemo- and enantioselective oxidations that are challenging for conventional reagents. Recent advances include the discovery of cold‐active and thermostable enzymes, the design of green reaction media, and the development of robust whole‐cell systems for preparative‐scale synthesis. Together, these innovations are expanding the role of enzymatic oxidations in fine chemicals, pharmaceutical intermediates and polymer precursors while minimising energy use and waste.

Research from Nature Portfolio

Engineering of monooxygenase-based Escherichia coli systems has enabled large-scale production of ester precursors from ricinoleic acid. Fusion of a polyionic tagging strategy with cofactor-regenerating modules allowed coexpression of a Baeyer–Villiger monooxygenase and a secondary alcohol dehydrogenase, achieving titres above 20 g L–1 in bench‐scale reactors and successful scale‐up to pilot volumes. Subsequent protein and process engineering targeted a single cysteine residue to boost oxidative and thermal stability, producing a variant capable of exceeding 41 g L–1 of the desired ester in under eight hours. This body of work exemplifies the seamless integration of enzyme redesign, metabolic engineering and bioprocess optimisation to deliver robust, high‐yielding oxidative biotransformations suited to industrial deployment.

Biocatalytic Oxidation Processes in Organic Synthesis publication trend

The graph below shows the total number of articles in biocatalytic oxidation processes in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Baeyer–Villiger monooxygenase (BVMO): An enzyme class that converts ketones into esters or lactones by inserting an oxygen atom, using a flavin cofactor and NADPH.

Flavin-dependent monooxygenase (FMO): An oxidoreductase that uses a flavin prosthetic group to incorporate one oxygen atom into an organic substrate while reducing the second to water.

Cofactor regeneration: A strategy to recycle essential cofactors such as NADPH in situ, ensuring continuous enzyme turnover without external cofactor addition.

Enantioselectivity: The ability of a catalyst to preferentially produce one enantiomer over its mirror image in a chiral product.

Whole-cell biocatalysis: The use of intact microbial cells, often recombinant, to perform enzymatic reactions without isolating the enzyme.

Regioselectivity: The preferential reaction of a reagent at one site over other possible sites within an organic molecule.

References

1. A Cold-Active Flavin-Dependent Monooxygenase from Janthinobacterium svalbardensis Unlocks Applications of Baeyer–Villiger Monooxygenases at Low Temperature. ACS Catalysis (2023).
2. Expanding the toolbox of Baeyer–Villiger and flavin monooxygenase biocatalysts for the enantiodivergent green synthesis of sulfoxides. Green Chemistry (2024).
3. Characterization and Crystal Structure of a Robust Cyclohexanone Monooxygenase. Angewandte Chemie International Edition (2016).
4. Engineering of Baeyer-Villiger monooxygenase-based Escherichia coli biocatalyst for large scale biotransformation of ricinoleic acid into (Z)-11-(heptanoyloxy)undec-9-enoic acid. Scientific Reports (2016).
5. Improving catalytic activity of the Baeyer–Villiger monooxygenase-based Escherichia coli biocatalysts for the overproduction of (Z)-11-(heptanoyloxy)undec-9-enoic acid from ricinoleic acid. Scientific Reports (2018).