Search for authorsSearch for similar articles
14
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cascades of Evolved Enzymes for the Synthesis of Complex Molecules

      1 , 2 , 1
      Angewandte Chemie International Edition
      Wiley

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Thanks to advances in enzyme discovery and protein engineering combined with the development of enzymatic multistep reaction cascades, new efficient routes for drug synthesis have been created that are superior to chemical syntheses. This supports the goal of the chemical and pharmaceutical industries to move to more sustainable and environmentally friendly processes. Recently described outstanding examples include the biocatalytic cascade syntheses of the cyclic dinucleotide MK‐1454, molnupiravir, and islatravir, as well as the efficient fixation of CO 2 to make starch using an artificial enzyme cascade.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: not found

          The cGAS–STING pathway as a therapeutic target in inflammatory diseases

          The cGAS–STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS–STING pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS–STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS–STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS–STING signalling cascade and discuss the general mechanisms underlying the association of cGAS–STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Biocatalysis: Enzymatic Synthesis for Industrial Applications

            Abstract Biocatalysis has found numerous applications in various fields as an alternative to chemical catalysis. The use of enzymes in organic synthesis, especially to make chiral compounds for pharmaceuticals as well for the flavors and fragrance industry, are the most prominent examples. In addition, biocatalysts are used on a large scale to make specialty and even bulk chemicals. This review intends to give illustrative examples in this field with a special focus on scalable chemical production using enzymes. It also discusses the opportunities and limitations of enzymatic syntheses using distinct examples and provides an outlook on emerging enzyme classes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Design of an in vitro biocatalytic cascade for the manufacture of islatravir

              Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.
                Bookmark

                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Angewandte Chemie International Edition
                Angew Chem Int Ed
                Wiley
                1433-7851
                1521-3773
                September 26 2022
                August 26 2022
                September 26 2022
                : 61
                : 39
                Affiliations
                [1 ] Department of Biochemical and Chemical Engineering TU Dortmund University Emil-Figge-Strasse 66 44227 Dortmund Germany
                [2 ] Institute of Biochemistry Department of Biotechnology & Enzyme Catalysis University of Greifswald Felix-Hausdorff-Strasse 4 17487 Greifswald Germany
                Article
                10.1002/anie.202208358
                5cd99d85-7106-4fea-b3d8-7635dbdbedee
                © 2022

                http://creativecommons.org/licenses/by/4.0/

                History

                Comments

                Comment on this article