Aug 2026· Biotechnology Advances· pp.
109024
· 0 citations· 114 references
Medicine
Abstract
Artificial enzymes represent transformative biocatalysts that overcome the inherent limitations of natural enzymes in substrate scope and activity specificity, enabling challenging new-to-nature reactions. Despite remarkable advances in designing diverse artificial enzymes through synthetic cofactor or non-canonical amino acid incorporation, their widespread industrial application remains hindered by the high costs and operational complexity of in vitro systems. Whole-cell biocatalysis emerges as a promising alternative by capitalizing on the cellular environment, including cofactor regeneration, multi-enzyme cascades, and enhanced enzyme stability. This review provides a comprehensive introduction to recent progress in artificial enzyme design and their successful applications in whole-cell biocatalysis. We summarize innovative protein engineering tools for creating artificial enzymes, assembly strategies to enhance in vivo catalytic performance, and representative applications of artificial enzymes-containing whole-cell systems in non-natural transformations. We also discuss the challenges and prospects of whole-cell artificial enzyme catalysis in advancing sustainable and scalable biomanufacturing.
The application repertoire of industrial biotechnology is constrained by the reaction scope of natural biocatalysis, which covers only a fraction of the accessible chemical space. To expand the versatility of biomanufacturing, abiological organometallic catalysts can be integrated into synthetic biology in the form of artificial metalloenzymes (ArMs). ArMs have been developed for a broad range of new-to-nature reactions, and in recent years multiple examples of their successful implementation in vivo have been demonstrated. Nevertheless, whole-cell ArM catalysis remains at the stage of fundamental research, and hybrid metabolic systems incorporating ArMs have yet to be realized at scale. In this review, we summarize the recent advances in whole-cell ArM catalysis and outline the challenges associated with in vivo ArM incorporation. We highlight the additional complexity that arises when transitioning from simple whole-cell biotransformations to metabolic engineering with ArMs and discuss potential strategies to achieve efficient integration of ArMs into biosynthetic pathways.
M. Slanska, T. Ward· Current Opinion in Chemical...· 0 citations
Artificial cell catalysts are emerging as programmable biocatalytic platforms for sustainable molecular conversion. By reconstituting enzymes and functional modules within synthetic compartments, they combine the selectivity of biological catalysis with the design flexibility of synthetic materials. For biotransformation, their main promise lies in the ability to coordinate reaction pathways, molecular transport, energy supply, spatial organization, and catalyst recovery within defined reaction spaces. Recent studies have shown that artificial compartments can support multienzyme conversion, selective transport, ATP and cofactor regeneration, hierarchical reaction architectures, and immobilized or flow-compatible operation. However, the engineering principles needed to translate these systems from proof-of-concept constructs into practical biotransformation platforms remain insufficiently integrated. In this review, we examine artificial cell catalysts from a bioengineering perspective, focusing on how catalytic and transport functions, energy and cofactor regeneration, spatial organization, and reactor implementation jointly determine process performance. This integrated view provides a framework for advancing artificial cell catalysts from cell-mimetic constructs toward quantitatively assessable and process-compatible biocatalytic systems.
Iori Kobayashi, S. Yoshimoto, K. Hori· Biotechnology and Bioenginee...· 0 citations
Biotransformation plays a crucial role in addressing global challenges related to resource utilization and energy sustainability. Natural processes, such as photosynthesis and microbial metabolism, transform external resources into functional compounds. However, these processes are often constrained by inefficiencies, slow reaction rates, and limited product diversity. Recent advancements across the physical, chemical, and biological sciences have led to the convergence of natural and artificial strategies that effectively tackle these challenges. These developments, alongside progress in artificial photosynthesis, offer solutions for CO2 reduction, N2 fixation, and sustainable chemical production, thereby broadening the scope of biotransformation beyond traditional natural processes. Herein, we first introduce recent representative achievements in resolving the structures and catalytic mechanisms of proteins/protein complexes/enzymes involved in natural biotransformation processes. Our review then highlights natural photosynthesis-inspired organic-biological hybrid systems, focusing on the conversion of CO2 and N2 as well as the diverse range of value-added products they enable. Furthermore, this paper will explore the potential of artificial photosynthesis systems, examining their integration and applications in advancing biotransformation processes. Finally, we discuss key challenges and propose future strategies to advance research in this field. The ongoing advancements in artificial systems hold immense promise for revolutionizing and paving the way for a sustainable future that extends beyond natural biotransformation.
Haotian Bai, Yan Zhang, Xu‐Bing Li et al.· National Science Review· 0 citations
Microbial biocatalysis spans biological platforms ranging from purified enzymes and multienzyme assemblies to electroenzymatic systems, whole-cell biocatalysts, and genetically programmable microbial cell factories. Yet despite their biological diversity, functional biocatalytic performance is often influenced by both catalytic activity and molecular accessibility. This recurring constraint highlights molecular accessibility as a common engineering consideration across microbial biocatalysis. Accordingly, this Review presents the concept of molecular access engineering as the rational control of molecular accessibility to improve functional biocatalytic performance across biological scales. The concept encompasses three complementary strategies governing molecular entry, intermediate transfer, and molecular exchange throughout biological systems. Examples from gas-converting enzymes, multienzyme assemblies, electroenzymatic systems, catalytic cascades, whole-cell biocatalysts, and microbial cell factories illustrate how engineering molecular accessibility can improve catalytic robustness, pathway efficiency, biological compatibility, and systems-level productivity. These examples therefore suggest that molecular access engineering has the potential to broaden the design space for microbial biocatalysis by complementing catalytic engineering.
Suk Min Kim· Journal of Microbiology and...· 0 citations
Biocatalysis, which combines green chemistry and white biotechnology, provides a sustainable alternative to conventional chemical synthesis. Enzymes and microbial systems act as selective, renewable catalysts, enabling complex reactions under mild conditions with minimal waste and high atom economy. In pharmaceuticals and fine chemicals, biocatalysis supports shorter synthetic routes, improved stereoselectivity, and regulatory compliance. Advances in enzyme engineering, such as directed evolution, rational design, and machine learning, have expanded the capabilities and robustness of biocatalysts. Techniques such as enzyme immobilization and whole-cell catalysis enhance stability and cost efficiency. Case studies, including simvastatin and pregabalin synthesis, showcase its practical benefits. The integration of chemoenzymatic strategies merges enzymatic precision with chemical versatility, streamlining synthesis. Aligned with the 12 principles of green chemistry, biocatalysis reduces hazardous reagents, lowers energy use, and enables renewable feedstocks. As regulatory bodies promote greener practices, its industrial adoption grows. Future directions include AI-guided enzyme discovery and continuous flow systems for scalable, eco-friendly production. This review explores the current landscape, key innovations, and future directions of biocatalysis in sustainable chemical manufacturing.
Keywords: Biocatalysis; Green Chemistry, White Biotechnology, Enzyme Engineering, Sustainable Synthesis, Biotransformation, Eco-friendly Catalysis
Sachin K Bhosale, S. Singh, N. Shinde et al.· Journal of Pharmaceutical Re...· 0 citations
Overall, the use of metagenomics, artificial intelligence, and experimental approaches has tremendous potential for developing efficient and economically viable lipases for sustainable biotechnological applications.
Km. Priti, Harish Chandra, Kalpana Sagar· Archives of Microbiology· 0 citations