New Advances in Chemoenzymatic Synthesis

The field of chemoenzymatic synthesis is rapidly evolving, offering innovative solutions for sustainable and efficient chemical production. By combining the selectivity of enzymatic catalysis with the versatility of chemical transformations, researchers have developed novel synthetic pathways that reduce environmental impacts while enhancing the yield and functional diversity. This approach leverages the strengths of chemical catalysis and biocatalysis, enabling the selective and eco-friendly syntheses of industrial and pharmaceutical compounds. A notable example is dynamic kinetic resolution, which allows for the efficient synthesis of enantiomerically pure compounds, overcoming the 50% yield limitation of traditional kinetic resolution [1]. These methods have already been successfully applied in the synthesis of active pharmaceutical ingredients (APIs), providing scalable and environmentally friendly alternatives to traditional routes. The integration of biocatalysis with process chemistry has paved the way for more efficient and cost-effective manufacturing strategies, with the potential to transform the chemical industry. Despite this progress, further improvements are needed to enhance catalysts’ compatibility, enzyme stability, and reaction efficiency [2]. However, the continuous progress in protein engineering and process optimization is expanding the scope of chemoenzymatic synthesis, driving the development of greener and more efficient chemical processes.

This Special Issue presents recent contributions that highlight key advances in chemoenzymatic synthesis, showcasing innovative approaches that promote progress in this field. The selected studies explore various aspects of chemoenzymatic processes, offering valuable insights into their development and application. Below is a summary of the main topics covered.

A chemoenzymatic process for producing epoxidized monoalkyl esters (EMAEs) from used soybean cooking oil (USCO) and fusel oil is described in the first article of this Special Issue [3]. This process involves three main steps: enzymatic hydrolysis of USCO using Candida rugosa lipase (CRL) to produce free fatty acids (FFAs), esterification of these FFAs with fusel oil using immobilized lipase Eversa^® Transform 2.0 to form monoalkyl esters (MAEs), and epoxidation of the MAEs using hydrogen peroxide and formic acid. This method demonstrates the potential for sustainable production of valuable oleochemicals from waste materials.

The second article describes the study of the β-mannanase enzyme from the blue mussel (Mytilus edulis), focusing on the roles of tryptophans W240 and W281 in substrate binding and catalytic activity [4]. Mutating these residues to alanine significantly reduced the enzymatic efficiency, particularly when both were substituted. W240 provided structural rigidity for mannosyl specificity, while W281 enhanced substrate binding through loop flexibility. The mutations also impaired transglycosylation with saccharides, but not with alcohols. This study highlights the critical role of tryptophans in enzyme function and their potential applications in novel compound synthesis.

The third article explores an enzyme that is involved in the processing of oligosaccharides. In particular, the enzyme β-mannosidase from Cellulomonas fimi (Cf-β-Man) and its immobilization for synthesizing β-mannosides were investigated [5]. The immobilized Cf-β-Man on IDA-Co²⁺-agarose significantly increased the efficiency of disaccharide synthesis compared with its soluble form (20% vs. 5% conversion) and exhibited improved stability and reusability, highlighting its potential in chemoenzymatic glycan synthesis.

The last two contributions are comprehensive reviews of sustainable chemoenzymatic approaches, emphasizing enzymatic and catalytic strategies for reducing environmental impacts and promoting circular economy principles.

In the fourth article, Markandan et al. report the current advancements in converting CO₂ into valuable chemicals such as methane, formic acid, and methanol through chemoenzymatic processes [6]. The article highlights the production of bicarbonates, bulk chemicals, synthetic fuels, and polymers as potential outcomes. It also discusses the challenges that are faced when implementing these processes and the prospects for future developments. Overall, it underscores the importance of chemoenzymatic CO₂ conversion in reducing carbon emissions and supporting sustainable development.

Article five discusses the potential of brewer’s spent grain (BSG), a byproduct of the brewing process, to be converted into valuable products such as xylooligosaccharides, xylitol, second-generation ethanol, biofilms, and furfural [7]. Various methods for extracting and processing hemicelluloses from BSG are reviewed, including the use of biocatalysts, homogeneous catalysts (acids, alkali, and salts), and heterogeneous catalysts (solid acids and metal oxides). The study highlights the significance of catalysts in optimizing reactions, improving market competitiveness, and reducing the environmental impact of production processes in biorefineries.

In conclusion, the Guest Editors hope that the articles in this Special Issue of Catalysts effectively showcase the dynamic nature of chemoenzymatic synthesis and its vast potential for sustainable processes. We sincerely thank the authors for their valuable contributions and the reviewers for their insightful comments, which helped improve the manuscripts. We also thank the editorial staff of Catalysts, with special gratitude to assistant editor Snowy Bian, for their dedication and exceptional work.