Biocatalysis at the heart of synthetic chemistry.
In synthetic chemistry, biocatalysis offers a technical solution for designing routes to produce simple to complex molecules. Considering the significant advances in the field of biotechnologies over the past two decades, the access to new ways of conducting chemical transformations and the emergence of numerous new enzymes have occurred. The landscape of attractive retrosynthetic disconnections to selectively build new bonds and design fundamentally new syntheses of (complex) molecular structures has significantly expanded. Moreover, enzymes are easy to handle and can operate in water-organic solvent mixtures or even without water. Ultimately, integrating enzymatic approaches may enlarge alternative routes and potential shortcuts.
The conciseness, environmental friendliness, and atom economy of synthetic methods have become important aspects of synthetic chemistry. Undeniably, biocatalysis aligns well with green and sustainable chemistry principles, offering efficient, economical, and low-waste alternatives over some traditional chemical synthesis. As a result, enzyme-driven processes have gained much more attention for the production of ever-increasing molecular complexity across numerous industries.
Enzyme-catalyzed chemistries involve using biocatalysts, such as enzymes soluble or immobilized or whole cells. This method, also known as biotransformation, leverages the precise selectivity of enzymes, making it valuable in industrial applications.  The stability and productivity of biocatalysts for commercial applications have already been well-demonstrated.
The science behind the enzyme from discovery, design to its production require a broad range of competencies, such as biochemistry, molecular biology, microbiology, protein engineering, bioinformatics, fermentation processes, bioengineering, computer science, material science. Their respective contribution has accelerated the ability to discover and engineer novel enzyme classes to build natural and unnatural molecules and will continue to expand.
In this dynamic field, the work contribution of academic researchers, start-ups and industry scientists have brought significant advances leading to innovative approaches and broaden the scope of synthetic methods and strategies. Overall, the synergy through fruitful collaborations and cross-fertilization of multiple competencies have never been so impactful for also translating the findings into commercial applications. Ultimately, we all share the same goal which is problem solving.
In this Special Issue, in which I have been honored to act as Guest Editor, I would like to thank all the authors and co-authors for their willingness to share their work and expertise covering very diverse areas of this fascinating discipline. It comprises fourteen mini reviews, articulated around three main topics briefly presented below.
Tools for enzyme optimization (articles 1–3):
In some cases, to match specific performance requirements, biocatalysts may need increased enzyme stability, catalytic efficiency, selectivity, and substrate scope. New strategies and tools such as protein engineering based on DNA recombination may be required to enhance the characteristics of natural enzymes to reach such high efficiency requirements. Along with computational tools, comprehensive understanding of the protein structure and dynamics in terms of molecular details or exploring the biodiversity are strategies that can significantly enhance the performance of enzymes. From an analytical point of view, to measure enzymatic activities, innovative methods are also being developed, especially when extensive studies through experimental tests are required and can be challenging.
Enzyme-catalyzed reactions (articles 4–9):
This edition covers a broad range of biotransformations, including oxidation, reduction, amination, amidation, nucleosides synthesis.  New strategies such as multi-catalysis has emerged to enhance the scope of synthetic protocols, including enzymatic cascade reactions, and hybrid catalysis by merging bio- and chemo-catalysis. Despite challenges that need to be addressed with respect to compatibility issues and catalyst reactivity ordering, recent studies show promising solutions.
Enzyme-based processes (articles 10–14):
Some pharmaceutical companies have been pioneers in the use and acceptance of biocatalysis for the unique properties that enzymes can deliver. Complemented by remarkable progress in bioprocess engineering, reaction engineering, or exploring new devices for continuous flow systems, process chemists are just beginning to take full advantage of the specificity with which enzymes react.
To tackle some limitations, innovative approaches exhibiting enzyme stability, activity and potentially reusability are being developed. These techniques include reactor design, enzyme immobilization, continuous flow process. These approaches are promising for the wide spread of industrial enzyme usage and ultimately reducing the production cost.
Within all chemistry disciplines, biocatalysis is only being slowly adopted, especially due to a lack of familiarity, some misconceptions and practical experience. Its awareness should be enhanced. Enzymatic catalysis is a mature technology and yet the full potential of this technology is to be unlocked, especially for reactions that are highly underexplored in enzyme catalysis or not yet known to the enzyme universe. This should encourage more chemists to take further ownership and expand applications in contemporary chemistry.
We hope that this special issue will be a source of inspiration for readers. There is a huge avenue for exploiting biocatalysis in synthetic chemistry!

Juliette Martin
SEQENS, Nîmes, France
juliette.martin@seqens.com