Biocatalysis and Enzyme Technology

Biocatalysis harnesses the extraordinary specificity and catalytic power of enzymes to drive chemical transformations under mild, environmentally benign conditions. Enzymes—nature’s catalysts—mediate bond formation and cleavage with unrivalled regio-, stereo- and chemoselectivity, often at ambient temperature and neutral pH. Recent decades have seen rapid advances in enzyme discovery, engineering and immobilisation, enabling applications in pharmaceuticals, fine chemicals, food, detergents and biofuels. Key enablers include high-throughput sequencing and screening to mine natural and metagenomic sources for novel activities; protein engineering and directed evolution to tailor substrate scope, stability and cofactor use; and reaction engineering strategies to integrate enzymes into continuous or cascade processes. The design of multi-step enzymatic cascades—both in vitro and in vivo—eliminates intermediate isolation, reduces waste and can shift equilibria to favour desired products. Complementing these efforts, computational tools now predict kinetic parameters and guide rational active-site modifications. Together, these developments are forging a sustainable, circular approach to chemical manufacture that reduces reliance on harsh reagents and high-energy processes.

Research from Nature Portfolio

A unified machine-learning framework has been developed to predict key enzyme kinetic parameters directly from protein sequence and substrate structure. The UniKP platform estimates turnover numbers (k_cat), Michaelis constants (K_m) and catalytic efficiencies, and can incorporate environmental factors such as pH and temperature. It has been demonstrated in enzyme discovery and directed-evolution projects, accelerating the identification of variants with improved activity for biocatalytic applications.

Site-specific incorporation of a non-canonical amino acid into a macrolide-tailoring cytochrome P450 has yielded variants capable of novel oxidation reactions on sugar-free macrolactone cores. Structural analyses revealed how a single aromatic substitution re-shapes the active-site hydrogen-bond network, reprogramming regioselectivity and enabling the biosynthetic pathway to be rewired for the generation of new antibiotic scaffolds.

Evolutionary and structural studies have traced the emergence of natural intermolecular Diels–Alderases from a flavin-dependent ancestor. Crystal structures, computational modelling and mutagenesis identified critical residues whose substitutions remodelled substrate binding, endowing the enzyme with high efficiency and enantioselectivity for [4+2] cycloaddition. This work illuminates principles for mining and engineering pericyclases to assemble complex ring systems.

Biocatalysis and Enzyme Technology publication trend

The graph below shows the total number of articles in biocatalysis and enzyme technology across all publications each year (not limited to Nature Index journals).

Technical terms

Biocatalysis: The use of enzymes or whole cells to accelerate chemical reactions with high selectivity and under mild conditions.

Enzyme cascade: A sequence of two or more enzyme-catalysed steps carried out in a single reaction vessel, often without intermediate isolation.

Directed evolution: Iterative rounds of random mutagenesis and selection to improve or alter enzyme properties.

Deep eutectic solvent (DES): A low-melting mixture of hydrogen-bond donors and acceptors, often biodegradable, used to stabilise enzymes and modulate solubility.

Non-canonical amino acid mutagenesis: The site‐specific incorporation of synthetic amino acids into proteins to introduce novel chemical functionality.

Pericyclase: An enzyme that catalyses pericyclic reactions such as Diels–Alder cycloadditions, enabling efficient ring construction.

References

1. UniKP: a unified framework for the prediction of enzyme kinetic parameters. Nature Communications (2023).
2. Unnatural activities and mechanistic insights of cytochrome P450 PikC gained from site-specific mutagenesis by non-canonical amino acids. Nature Communications (2023).
3. The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba. Nature Communications (2024).
4. Recombinant GH3 β-glucosidase stimulated by xylose and tolerant to furfural and 5-hydroxymethylfurfural obtained from Aspergillus nidulans. Bioresources and Bioprocessing (2024).
5. Stabilization of Non-Native Folds and Programmable Protein Gelation in Compositionally Designed Deep Eutectic Solvents. ACS Nano (2024).
6. Deep Eutectic Solvents for the Enzymatic Synthesis of Sugar Esters: A Generalizable Strategy?. ACS Sustainable Chemistry & Engineering (2023).